DOCSLIB.ORG

The Microarray Data Analysis Results from the Performed Comparative

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Microarray Data Analysis Results from the Performed Comparative Supplementary table 3: The microarray data analysis results from the performed comparative analyses between controls, patients before and after infliximab treatment in UC, CDc, IBDc and CDi [fold change (FC), average log2 gene expression level across all arrays involved in the comparative analysis (AveExpr), p-value and FDR] for the filtered probe sets (probe sets with an intensity > log2(50) in at least 10% of the samples) representing MMP, TIMP, ADAM(TS) and growth factor genes. R: responders, NR: non-responders. The abbreviations of the tissue remodeling genes are explained in supplementary table 1. Probe Set ID Gene Symbol UC before therapy (n=24) CDi before therapy (n=18) vs vs CDc before therapy (n=19) CDc before therapy (n=19) FC AveExpr p-value FDR FC AveExpr p-value FDR MMP genes 204475_at MMP1 0.92 10.38 0.82 0.98 1.12 10.53 0.76 0.92 201069_at MMP2 1.01 8.08 0.98 1.00 0.80 7.92 0.46 0.75 205828_at MMP3 1.01 10.42 0.97 1.00 0.47 9.88 0.08 0.30 204259_at MMP7 1.97 8.32 0.02 0.46 0.44 7.20 0.01 0.06 203936_s_at MMP9 1.06 8.07 0.79 0.98 0.46 7.47 0.01 0.06 205680_at MMP10 1.76 6.94 0.09 0.71 0.52 6.03 0.10 0.36 204580_at MMP12 1.27 10.91 0.19 0.81 0.38 10.05 0.00 0.03 160020_at MMP14 1.17 6.41 0.05 0.60 0.97 6.26 0.60 0.83 202827_s_at MMP14 1.30 5.98 0.06 0.65 0.90 5.69 0.45 0.75 202828_s_at MMP14 1.17 6.45 0.08 0.69 0.98 6.31 0.86 0.95 203365_s_at MMP15 0.99 6.76 0.91 0.99 1.18 6.88 0.09 0.33 204574_s_at MMP19 1.01 5.52 0.89 0.99 1.03 5.54 0.58 0.82 204575_s_at MMP19 1.12 5.67 0.54 0.94 0.78 5.40 0.23 0.54 227106_at MMP19 1.02 5.54 0.67 0.96 1.08 5.58 0.11 0.36 221953_s_at MMP24 /// LOC729580 0.96 7.01 0.56 0.94 1.02 7.06 0.71 0.89 49679_s_at MMP24 /// LOC729580 0.98 6.81 0.63 0.96 1.02 6.85 0.70 0.89 207890_s_at MMP25 1.14 5.71 0.06 0.65 1.09 5.67 0.36 0.68 219909_at MMP28 0.99 5.05 0.97 1.00 0.90 4.99 0.41 0.72 222937_s_at MMP28 1.04 5.92 0.53 0.94 0.96 5.85 0.60 0.84 224207_x_at MMP28 1.02 6.79 0.69 0.96 1.04 6.80 0.61 0.84 239272_at MMP28 0.86 6.21 0.18 0.80 0.86 6.22 0.12 0.38 239273_s_at MMP28 0.94 6.31 0.55 0.94 0.88 6.27 0.18 0.48 TIMP genes 201666_at TIMP1 1.51 10.55 0.01 0.42 0.63 9.89 0.04 0.19 203167_at TIMP2 1.31 6.72 0.04 0.57 1.15 6.60 0.26 0.58 224560_at TIMP2 1.21 7.89 0.27 0.86 0.92 7.68 0.67 0.87 231579_s_at TIMP2 1.24 9.08 0.22 0.83 0.98 8.89 0.93 0.98 201147_s_at TIMP3 1.07 4.84 0.68 0.96 0.79 4.61 0.19 0.50 201148_s_at TIMP3 1.09 6.43 0.22 0.83 0.92 6.31 0.24 0.55 201149_s_at TIMP3 1.07 5.26 0.71 0.97 0.75 5.00 0.14 0.43 201150_s_at TIMP3 1.27 6.09 0.25 0.84 0.69 5.64 0.16 0.45 ADAM genes 205180_s_at ADAM8 1.09 5.77 0.47 0.93 1.06 5.75 0.66 0.87 1555326_a_at ADAM9 1.40 7.72 0.03 0.55 0.69 7.19 0.05 0.22 202381_at ADAM9 1.19 10.04 0.08 0.68 0.83 9.77 0.10 0.36 202604_x_at ADAM10 1.16 6.61 0.14 0.77 0.86 6.39 0.20 0.50 214895_s_at ADAM10 1.06 6.61 0.68 0.96 0.79 6.40 0.13 0.40 1555896_a_at ADAM15 1.06 6.91 0.34 0.89 0.81 6.72 0.00 0.04 217007_s_at ADAM15 1.07 5.86 0.41 0.91 0.80 5.65 0.03 0.16 205745_x_at ADAM17 0.98 6.19 0.69 0.96 0.89 6.12 0.11 0.36 209765_at ADAM19 1.11 6.19 0.41 0.91 0.81 5.96 0.16 0.45 205997_at ADAM28 1.32 6.03 0.14 0.77 1.46 6.07 0.08 0.31 208269_s_at ADAM28 1.11 5.35 0.06 0.63 1.04 5.30 0.47 0.76 233868_x_at ADAM33 1.00 6.76 0.97 1.00 1.09 6.82 0.40 0.71 206134_at ADAMDEC1 0.65 8.30 0.02 0.48 1.16 8.75 0.41 0.71 222162_s_at ADAMTS1 1.28 5.74 0.31 0.88 0.73 5.32 0.21 0.53 235368_at ADAMTS5 1.05 5.45 0.69 0.96 1.42 5.65 0.01 0.08 220705_s_at ADAMTS7 1.02 5.41 0.84 0.98 1.15 5.50 0.13 0.40 226814_at ADAMTS9 1.40 6.53 0.02 0.45 0.62 5.92 0.00 0.03 220208_at ADAMTS13 0.97 5.73 0.56 0.94 0.89 5.67 0.04 0.18 Growth factor genes 212285_s_at AGRN 1.19 6.85 0.03 0.52 0.85 6.59 0.06 0.25 217410_at AGRN 1.10 5.41 0.17 0.79 1.02 5.34 0.79 0.92 217419_x_at AGRN 1.14 6.61 0.10 0.73 0.82 6.36 0.03 0.16 202834_at AGT 1.33 5.90 0.05 0.60 1.00 5.66 0.98 0.99 213001_at ANGPTL2 1.07 6.60 0.75 0.97 0.73 6.33 0.17 0.47 213004_at ANGPTL2 1.02 5.04 0.88 0.99 0.78 4.85 0.12 0.38 221009_s_at ANGPTL4 1.50 6.16 0.00 0.20 1.29 6.01 0.06 0.26 223333_s_at ANGPTL4 1.32 5.37 0.02 0.49 1.21 5.29 0.15 0.43 205239_at AREG 1.42 8.63 0.04 0.60 0.23 7.31 0.00 0.00 210237_at ARTN 1.01 5.66 0.85 0.98 0.82 5.51 0.01 0.06 202701_at BMP1 0.95 6.07 0.42 0.91 0.91 6.04 0.08 0.31 205574_x_at BMP1 1.06 5.56 0.57 0.95 0.84 5.39 0.08 0.30 206725_x_at BMP1 1.08 5.36 0.23 0.83 1.03 5.32 0.71 0.89 207595_s_at BMP1 1.01 5.70 0.86 0.99 0.86 5.58 0.04 0.19 205289_at BMP2 1.11 8.88 0.31 0.88 0.42 8.19 0.00 0.00 205290_s_at BMP2 1.19 8.21 0.12 0.74 0.42 7.46 0.00 0.00 211518_s_at BMP4 1.11 5.52 0.17 0.80 0.98 5.42 0.75 0.91 211260_at BMP7 0.94 5.79 0.13 0.76 0.99 5.83 0.84 0.94 220203_at BMP8A 1.01 5.55 0.88 0.99 0.98 5.53 0.76 0.92 218529_at CD320 1.07 7.10 0.27 0.86 0.67 6.77 0.00 0.00 219505_at CECR1 1.19 7.29 0.32 0.88 0.66 6.86 0.03 0.15 219500_at CLCF1 1.15 5.59 0.03 0.52 0.90 5.40 0.07 0.29 207442_at CSF3 1.18 6.03 0.28 0.86 1.00 5.90 0.99 1.00 209101_at CTGF 1.32 7.64 0.11 0.73 0.42 6.82 0.00 0.00 205767_at EREG 1.75 6.65 0.04 0.56 0.40 5.56 0.01 0.06 218255_s_at FBRS 1.01 6.09 0.89 0.99 1.09 6.14 0.10 0.34 204421_s_at FGF2 1.11 5.18 0.36 0.90 0.79 4.93 0.04 0.19 208417_at FGF6 1.04 5.52 0.39 0.91 1.03 5.51 0.61 0.84 1554741_s_at FGF7 /// KGFLP1 /// 1.13 5.00 0.64 0.96 0.68 4.62 0.16 0.45 KGFLP2 206404_at FGF9 0.70 4.60 0.00 0.26 2.57 5.55 0.00 0.00 221136_at GDF2 1.05 5.85 0.38 0.90 1.05 5.85 0.35 0.67 206614_at GDF5 0.99 5.80 0.89 0.99 1.02 5.82 0.71 0.89 221577_x_at GDF15/// LOC100287132 1.18 6.52 0.20 0.82 0.61 6.03 0.00 0.02 /// LOC100292463 202543_s_at GMFB 0.98 8.31 0.81 0.98 0.74 8.11 0.00 0.04 202544_at GMFB 0.90 8.77 0.02 0.49 0.94 8.81 0.29 0.61 204220_at GMFG 1.18 7.09 0.30 0.87 0.88 6.87 0.49 0.77 208308_s_at GPI 1.07 9.76 0.22 0.83 0.83 9.58 0.01 0.06 200678_x_at GRN 0.93 9.16 0.32 0.88 0.79 9.05 0.00 0.03 211284_s_at GRN 0.97 8.47 0.62 0.95 0.83 8.37 0.01 0.10 216041_x_at GRN 0.95 9.13 0.47 0.93 0.79 9.00 0.00 0.03 203821_at HBEGF 1.56 7.57 0.04 0.57 0.51 6.74 0.01 0.05 38037_at HBEGF 1.49 7.31 0.05 0.62 0.61 6.64 0.02 0.11 200896_x_at HDGF 1.10 9.32 0.02 0.47 1.23 9.39 0.00 0.01 216484_x_at HDGF 1.04 8.56 0.24 0.84 1.17 8.63 0.01 0.05 209524_at HDGFRP3 1.03 5.73 0.89 0.99 0.59 5.34 0.02 0.11 209526_s_at HDGFRP3 0.97 5.45 0.81 0.98 0.64 5.17 0.01 0.07 216693_x_at HDGFRP3 0.94 5.60 0.67 0.96 0.61 5.30 0.01 0.05 211577_s_at IGF1 1.02 5.60 0.73 0.97 0.99 5.57 0.80 0.93 202409_at IGF2 /// INS-IGF2 1.06 5.11 0.69 0.97 1.07 5.12 0.66 0.87 210511_s_at INHBA 1.19 5.72 0.56 0.94 0.92 5.52 0.81 0.93 209098_s_at JAG1 1.21 6.66 0.15 0.78 0.53 6.06 0.00 0.01 209099_x_at JAG1 1.10 10.29 0.14 0.77 0.64 9.89 0.00 0.00 216268_s_at JAG1 1.10 10.30 0.18 0.80 0.60 9.87 0.00 0.00 231183_s_at JAG1 0.98 6.00 0.89 0.99 0.56 5.62 0.00 0.02 209784_s_at JAG2 1.13 5.33 0.06 0.64 1.30 5.41 0.00 0.02 32137_at JAG2 1.08 5.75 0.28 0.86 1.34 5.89 0.00 0.02 226534_at KITLG 0.69 7.83 0.00 0.16 0.71 7.89 0.00 0.04 206268_at LEFTY1 0.68 8.99 0.03 0.52 0.06 7.33 0.00 0.00 205266_at LIF 1.36 5.99 0.00 0.19 0.87 5.64 0.07 0.29 1559361_at MACC1 1.15 4.29 0.12 0.75 2.17 4.72 0.00 0.00 1566764_at MACC1 1.27 3.85 0.09 0.70 3.31 4.49 0.00 0.00 1566766_a_at MACC1 1.22 5.24 0.00 0.22 2.30 5.67 0.00 0.00 232151_at MACC1 1.15 4.98 0.12 0.75 2.50 5.51 0.00 0.00 202655_at MANF 1.14 9.29 0.02 0.45 0.74 8.97 0.00 0.00 209035_at MDK 0.89 8.01 0.36 0.90 1.37 8.33 0.02 0.13 206560_s_at MIA 1.12 6.12 0.43 0.92 0.90 5.95 0.40 0.71 205614_x_at MST1 1.02 6.25 0.75 0.97 2.41 6.85 0.00 0.00 216320_x_at MST1 1.04 6.27 0.61 0.95 2.69 6.94 0.00 0.00 214075_at NENF 0.97 5.92 0.63 0.96 0.89 5.85 0.02 0.13 218407_x_at NENF 0.98 7.89 0.57 0.95 0.92 7.85 0.10 0.34 208232_x_at NRG1 1.09 5.17 0.15 0.78 1.00 5.10 0.99 1.00 230329_s_at NUDT6 0.77 6.13 0.00 0.26 0.64 6.02 0.00 0.00 219475_at OSGIN1 1.07 5.34 0.32 0.88 1.48 5.56 0.00 0.00 214637_at OSM 1.15 5.21 0.25 0.84 1.11 5.17 0.50 0.78 230170_at OSM 1.50 5.08 0.10 0.71 1.21 4.89 0.50 0.78 205463_s_at PDGFA 0.99 7.02 0.88 0.99 1.11 7.10 0.12 0.39 216867_s_at PDGFA 1.02 5.15 0.79 0.98 1.15 5.23 0.14 0.42 229830_at PDGFA 0.89 7.80 0.22 0.83 1.13 7.98 0.18 0.48 216061_x_at PDGFB 1.10 5.51 0.04 0.60 1.00 5.43 0.93 0.98 218718_at PDGFC 1.00 5.35 0.99 1.00 2.03 5.85 0.00 0.00 225064_at RABEP1 1.04 6.42 0.54 0.94 1.00 6.39 1.00 1.00 225092_at RABEP1 1.12 6.79 0.17 0.79 1.11 6.78 0.28 0.60 219057_at RABEP2 1.02 5.50 0.67 0.96 1.14 5.58 0.03 0.16 74694_s_at RABEP2 0.89 6.38 0.10 0.73 1.07 6.51 0.33 0.65 77508_r_at RABEP2 1.00 6.42 0.98 1.00 1.03 6.44 0.59 0.83 209752_at REG1A 0.65 11.45 0.31 0.88 2.84 12.53 0.01 0.07 206286_s_at TDGF1 /// TDGF3 0.93 5.89 0.62 0.95 0.51 5.47 0.00 0.00 205009_at TFF1 1.59 12.12 0.00 0.20 1.25 11.90 0.23 0.54 214476_at TFF2 1.48 7.45 0.08 0.68 1.86 7.57 0.11 0.36 204623_at TFF3 0.88 11.37 0.22 0.83 1.12 11.56 0.21 0.52 205016_at TGFA 0.94 7.34 0.59 0.95 1.07 7.43 0.52 0.79 211258_s_at TGFA 0.98 5.39 0.73 0.97 0.98 5.39 0.61 0.84 203085_s_at TGFB1 1.20 5.69 0.38 0.90 0.99 5.54 0.95 0.99 204858_s_at TYMP 1.14 7.27 0.20 0.82 1.10 7.24 0.39 0.70 210512_s_at VEGFA 1.25 9.23 0.01 0.35 1.21 9.18 0.02 0.14 210513_s_at VEGFA 1.31 6.52 0.01 0.31 1.15 6.40 0.15 0.43 211527_x_at VEGFA 1.39 6.16 0.00 0.19 1.11 5.97 0.29 0.61 212171_x_at VEGFA 1.26 7.22 0.00 0.15 1.12 7.11 0.08 0.30 209946_at VEGFC 1.04 4.89 0.77 0.98 1.01 4.86 0.96 0.99 205586_x_at VGF 1.11 5.29 0.06 0.64 1.06 5.25 0.25 0.57 Probe Set ID Gene Symbol UC before therapy CDc before therapy IBDc before therapy CDi before therapy (n=24) (n=19) (n=43) (n=18) vs vs vs vs control colons control colons control colons control ileums (n=6) (n=6) (n=6) (n=6)
Load more

Recommended publications
  • Role of Cyclosporine in Gingival Hyperplasia: an in Vitro Study on Gingival Fibroblasts
    International Journal of Molecular Sciences Article Role of Cyclosporine in Gingival Hyperplasia: An In Vitro Study on Gingival Fibroblasts 1, , 2, 3 3 Dorina Lauritano * y , Annalisa Palmieri y, Alberta Lucchese , Dario Di Stasio , Giulia Moreo 1 and Francesco Carinci 4 1 Department of Medicine and Surgery, Centre of Neuroscience of Milan, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] 2 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, via Belmoro 8, 40126 Bologna, Italy; [email protected] 3 Multidisciplinary Department of Medical and Dental Specialties, University of Campania-Luigi Vanvitelli, 80138 Naples, Italy; [email protected] (A.L.); [email protected] (D.D.S.) 4 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-335-679-0163 These authors contributed equally to this work. y Received: 25 November 2019; Accepted: 13 January 2020; Published: 16 January 2020 Abstract: Background: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. Materials and methods: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control.
    [Show full text]
  • Gene Symbol Category ACAN ECM ADAM10 ECM Remodeling-Related ADAM11 ECM Remodeling-Related ADAM12 ECM Remodeling-Related ADAM15 E
    Supplementary Material (ESI) for Integrative Biology This journal is (c) The Royal Society of Chemistry 2010 Gene symbol Category ACAN ECM ADAM10 ECM remodeling-related ADAM11 ECM remodeling-related ADAM12 ECM remodeling-related ADAM15 ECM remodeling-related ADAM17 ECM remodeling-related ADAM18 ECM remodeling-related ADAM19 ECM remodeling-related ADAM2 ECM remodeling-related ADAM20 ECM remodeling-related ADAM21 ECM remodeling-related ADAM22 ECM remodeling-related ADAM23 ECM remodeling-related ADAM28 ECM remodeling-related ADAM29 ECM remodeling-related ADAM3 ECM remodeling-related ADAM30 ECM remodeling-related ADAM5 ECM remodeling-related ADAM7 ECM remodeling-related ADAM8 ECM remodeling-related ADAM9 ECM remodeling-related ADAMTS1 ECM remodeling-related ADAMTS10 ECM remodeling-related ADAMTS12 ECM remodeling-related ADAMTS13 ECM remodeling-related ADAMTS14 ECM remodeling-related ADAMTS15 ECM remodeling-related ADAMTS16 ECM remodeling-related ADAMTS17 ECM remodeling-related ADAMTS18 ECM remodeling-related ADAMTS19 ECM remodeling-related ADAMTS2 ECM remodeling-related ADAMTS20 ECM remodeling-related ADAMTS3 ECM remodeling-related ADAMTS4 ECM remodeling-related ADAMTS5 ECM remodeling-related ADAMTS6 ECM remodeling-related ADAMTS7 ECM remodeling-related ADAMTS8 ECM remodeling-related ADAMTS9 ECM remodeling-related ADAMTSL1 ECM remodeling-related ADAMTSL2 ECM remodeling-related ADAMTSL3 ECM remodeling-related ADAMTSL4 ECM remodeling-related ADAMTSL5 ECM remodeling-related AGRIN ECM ALCAM Cell-cell adhesion ANGPT1 Soluble factors and receptors
    [Show full text]
  • Extracellular Matrix Alterations in Metastatic Processes
    International Journal of Molecular Sciences Review Extracellular Matrix Alterations in Metastatic Processes Mayra Paolillo * and Sergio Schinelli Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy; [email protected] * Correspondence: [email protected] Received: 17 September 2019; Accepted: 30 September 2019; Published: 7 October 2019 Abstract: The extracellular matrix (ECM) is a complex network of extracellular-secreted macromolecules, such as collagen, enzymes and glycoproteins, whose main functions deal with structural scaffolding and biochemical support of cells and tissues. ECM homeostasis is essential for organ development and functioning under physiological conditions, while its sustained modification or dysregulation can result in pathological conditions. During cancer progression, epithelial tumor cells may undergo epithelial-to-mesenchymal transition (EMT), a morphological and functional remodeling, that deeply alters tumor cell features, leading to loss of epithelial markers (i.e., E-cadherin), changes in cell polarity and intercellular junctions and increase of mesenchymal markers (i.e., N-cadherin, fibronectin and vimentin). This process enhances cancer cell detachment from the original tumor mass and invasiveness, which are necessary for metastasis onset, thus allowing cancer cells to enter the bloodstream or lymphatic flow and colonize distant sites. The mechanisms that lead to development of metastases in specific sites are still largely obscure but modifications occurring in target tissue ECM are being intensively studied. Matrix metalloproteases and several adhesion receptors, among which integrins play a key role, are involved in metastasis-linked ECM modifications. In addition, cells involved in the metastatic niche formation, like cancer associated fibroblasts (CAF) and tumor associated macrophages (TAM), have been found to play crucial roles in ECM alterations aimed at promoting cancer cells adhesion and growth.
    [Show full text]
  • Expression Profiling of Metalloproteinases and Their
    Available online http://arthritis-research.com/content/8/4/R124 ResearchVol 8 No 4 article Open Access Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage Rose K Davidson1, Jasmine G Waters1, Lara Kevorkian1, Clare Darrah2, Adele Cooper2, Simon T Donell2 and Ian M Clark1 1School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK 2Institute of Orthopaedics, Norfolk and Norwich University Hospital, Norwich NR4 7UY, UK Corresponding author: Ian M Clark, [email protected] Received: 24 May 2006 Revisions requested: 19 Jun 2006 Revisions received: 11 Jul 2006 Accepted: 14 Jul 2006 Published: 19 Jul 2006 Arthritis Research & Therapy 2006, 8:R124 (doi:10.1186/ar2013) This article is online at: http://arthritis-research.com/content/8/4/R124 © 2006 Davidson et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Cartilage destruction in osteoarthritis (OA) is thought to be The four most significantly upregulated genes (P < 0.0001) in mediated by two main enzyme families; the matrix OA synovium compared to the fractured NOF are MMP28, metalloproteinases (MMPs) are responsible for cartilage ADAMTS16, ADAMTS17 and TIMP2. For MMP9, MMP10, collagen breakdown, whereas enzymes from the 'a disintegrin MMP12, MMP17, MMP23, MMP28, ADAMTS4, and and metalloproteinase domain with thrombospondin motifs' ADAMTS9, there is a significant correlation between expression (ADAMTS) family mediate cartilage aggrecan loss. Tissue levels in the synovium and cartilage, suggesting similar inhibitors of metalloproteinases (TIMPs) regulate the activity of mechanisms of regulation.
    [Show full text]
  • Matrisome-Associated Gene Expression Patterns Correlating with TIMP2 in Cancer David Peeney1*, Yu Fan2, Trinh Nguyen 2, Daoud Meerzaman2 & William G
    www.nature.com/scientificreports OPEN Matrisome-Associated Gene Expression Patterns Correlating with TIMP2 in Cancer David Peeney1*, Yu Fan2, Trinh Nguyen 2, Daoud Meerzaman2 & William G. Stetler-Stevenson 1 Remodeling of the extracellular matrix (ECM) to facilitate invasion and metastasis is a universal hallmark of cancer progression. However, a defnitive therapeutic target remains to be identifed in this tissue compartment. As major modulators of ECM structure and function, matrix metalloproteinases (MMPs) are highly expressed in cancer and have been shown to support tumor progression. MMP enzymatic activity is inhibited by the tissue inhibitor of metalloproteinase (TIMP1–4) family of proteins, suggesting that TIMPs may possess anti-tumor activity. TIMP2 is a promiscuous MMP inhibitor that is ubiquitously expressed in normal tissues. In this study, we address inconsistencies in the literature regarding the role of TIMP2 in tumor progression by analyzing co-expressed genes in tumor vs. normal tissue. Utilizing data from The Cancer Genome Atlas and Genotype-Tissue expression studies, focusing on breast and lung carcinomas, we analyzed the correlation between TIMP2 expression and the transcriptome to identify a list of genes whose expression is highly correlated with TIMP2 in tumor tissues. Bioinformatic analysis of the identifed gene list highlights a core of matrix and matrix- associated genes that are of interest as potential modulators of TIMP2 function, thus ECM structure, identifying potential tumor microenvironment biomarkers and/or therapeutic targets for further study. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are the major mediators of extracellular matrix (ECM) breakdown and turnover. Humans express 23 MMPs and these play a critical role in tissue development, homeostasis and disease progression.
    [Show full text]
  • Biochemical Characterization and Zinc Binding Group (Zbgs) Inhibition Studies on the Catalytic Domains of Mmp7 (Cdmmp7) and Mmp16 (Cdmmp16)
    MIAMI UNIVERSITY The Graduate School Certificate for Approving the Dissertation We hereby approve the Dissertation of Fan Meng Candidate for the Degree DOCTOR OF PHILOSOPHY ______________________________________ Director Dr. Michael W. Crowder ______________________________________ Dr. David L. Tierney ______________________________________ Dr. Carole Dabney-Smith ______________________________________ Dr. Christopher A. Makaroff ______________________________________ Graduate School Representative Dr. Hai-Fei Shi ABSTRACT BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) by Fan Meng Matrix metalloproteinase 7 (MMP7/matrilysin-1) and membrane type matrix metalloproteinase 16 (MMP16/MT3-MMP) have been implicated in the progression of pathological events, such as cancer and inflammatory diseases; therefore, these two MMPs are considered as viable drug targets. In this work, we (a) provide a review of the role(s) of MMPs in biology and of the previous efforts to target MMPs as therapeutics (Chapter 1), (b) describe our efforts at over-expression, purification, and characterization of the catalytic domains of MMP7 (cdMMP7) and MMP16 (cdMMP16) (Chapters 2 and 3), (c) present our efforts at the preparation and initial spectroscopic characterization of Co(II)-substituted analogs of cdMMP7 and cdMMP16 (Chapters 2 and 3), (d) present inhibition data on cdMMP7 and cdMMP16 using zinc binding groups (ZBG) as potential scaffolds for future inhibitors (Chapter 3), and (e) summarize our data in the context of previous results and suggest future directions (Chapter 4). The work described in this dissertation integrates biochemical (kinetic assays, inhibition studies, limited computational methods), spectroscopic (CD, UV-Vis, 1H-NMR, fluorescence, and EXAFS), and analytical (MALDI-TOF mass spectrometry, isothermal calorimetry) methods to provide a detailed structural and mechanistic view of these MMPs.
    [Show full text]
  • A Genomic Analysis of Rat Proteases and Protease Inhibitors
    A genomic analysis of rat proteases and protease inhibitors Xose S. Puente and Carlos López-Otín Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain Send correspondence to: Carlos López-Otín Departamento de Bioquímica y Biología Molecular Facultad de Medicina, Universidad de Oviedo 33006 Oviedo-SPAIN Tel. 34-985-104201; Fax: 34-985-103564 E-mail: [email protected] Proteases perform fundamental roles in multiple biological processes and are associated with a growing number of pathological conditions that involve abnormal or deficient functions of these enzymes. The availability of the rat genome sequence has opened the possibility to perform a global analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into five catalytic classes: 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. Overall, this distribution is similar to that of the mouse degradome, but significatively more complex than that corresponding to the human degradome composed of 561 proteases and homologs. This increased complexity of the rat protease complement mainly derives from the expansion of several gene families including placental cathepsins, testases, kallikreins and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in the rat and mouse genomes and may contribute to explain some functional differences between these two closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with the mouse protease inhibitor complement and the marked expansion of families of cysteine and serine protease inhibitors in rat and mouse with respect to human.
    [Show full text]
  • MT5-MMP Controls APP and Β-CTF/C99 Metabolism Through Proteolytic-Dependent and -Independent Mechanisms Relevant for Alzheimer’S Disease
    bioRxiv preprint doi: https://doi.org/10.1101/2020.09.01.258665; this version posted September 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. MT5-MMP controls APP and β-CTF/C99 metabolism through proteolytic-dependent and -independent mechanisms relevant for Alzheimer’s disease Laura García-González 1, Jean-Michel Paumier 1,a, Laurence Louis 1, Dominika Pilat 1, Anne Bernard 1, Delphine Stephan 1, Nicolas Jullien 1, Frédéric Checler 2, Emmanuel Nivet 1, Michel 1 1, 1, Khrestchatisky , Kévin Baranger * and Santiago Rivera * + 1. Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France. 2. IPMC, UMR 7275 CNRS-UCA, Labex DistAlz, 06560 Valbonne, France. a. Present address: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. * Equally corresponding authors and responsible for the supervision of the study: kevin.baranger@univ- amu.fr and [email protected] Institute of Neuropathophysiology (INP) UMR 7051, CNRS - Aix-Marseille Université Campus Timone 27 Bld Jean Moulin 13005 Marseille France Tel: 33 4 91 69 87 71 Tel: 33 4 91 69 89 64 Fax: 33 4 91 25 89 70 Running title: MT5-MMP controls C99 fate bioRxiv preprint doi: https://doi.org/10.1101/2020.09.01.258665; this version posted September 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT We previously discovered the implication of membrane-type 5-matrix metalloproteinase (MT5-MMP) in Alzheimer’s disease AD pathogenesis.
    [Show full text]
  • Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 As Potential Molecular Markers in Advanced Human Gastric Cancer
    Hindawi Publishing Corporation Disease Markers Volume 2014, Article ID 285906, 9 pages http://dx.doi.org/10.1155/2014/285906 Research Article Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 as Potential Molecular Markers in Advanced Human Gastric Cancer Sol de la Peña,1 Clara Luz Sampieri,2 Mariana Ochoa-Lara,3 Kenneth León-Córdoba,4 and José María Remes-Troche5 1 Biomedical Sciences Doctoral Program, Biomedical Research Center, University of Veracruz, 91190 Xalapa, Veracruz, Mexico 2 Institute of Public Health, University of Veracruz, 91190 Xalapa, Veracruz, Mexico 3 Public Health Master Program, University of Veracruz, 91190 Xalapa, Veracruz, Mexico 4 Dr. Miguel Dorantes Mesa Hospital, 91130 Xalapa, Veracruz, Mexico 5 Medical-Biological Research Institute, University of Veracruz, 91700 Veracruz, Veracruz, Mexico Correspondence should be addressed to Clara Luz Sampieri; [email protected] Received 9 February 2013; Accepted 27 November 2013; Published 11 February 2014 Academic Editor: Stamatios Theocharis Copyright © 2014 Sol de la Pena˜ et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. During progression of gastric cancer (GC), degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs): changes in the expression of these have been related to unfavorable prognosis in GC. Objective. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC. Methods. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle () values, as very high ( ≤25), high ( =26–30), moderate ( =31–35), low ( =36–39), or not detected ( =40).
    [Show full text]
  • Figure S1. Gene Ontology Classification of Abeliophyllum Distichum Leaves Extract-Induced Degs
    Figure S1. Gene ontology classification of Abeliophyllum distichum leaves extract-induced DEGs. The results are summarized in three main categories: Biological process, Cellular component and Molecular function. Figure S2. KEGG pathway enrichment analysis using Abeliophyllum distichum leaves extract-DEGs (A). Venn diagram analysis of DEGs involved in PI3K/Akt signaling pathway and Rap1 signaling pathway (B). Figure S3. The expression (A) and protein levels (B) of Akt3 in AL-treated SK-MEL2 cells. Values with different superscripted letters are significantly different (p < 0.05). Table S1. Abeliophyllum distichum leaves extract-induced DEGs. log2 Fold Gene name Gene description Change A2ML1 alpha-2-macroglobulin-like protein 1 isoform 2 [Homo sapiens] 3.45 A4GALT lactosylceramide 4-alpha-galactosyltransferase [Homo sapiens] −1.64 ABCB4 phosphatidylcholine translocator ABCB4 isoform A [Homo sapiens] −1.43 ABCB5 ATP-binding cassette sub-family B member 5 isoform 1 [Homo sapiens] −2.99 ABHD17C alpha/beta hydrolase domain-containing protein 17C [Homo sapiens] −1.62 ABLIM2 actin-binding LIM protein 2 isoform 1 [Homo sapiens] −2.53 ABTB2 ankyrin repeat and BTB/POZ domain-containing protein 2 [Homo sapiens] −1.48 ACACA acetyl-CoA carboxylase 1 isoform 1 [Homo sapiens] −1.76 ACACB acetyl-CoA carboxylase 2 precursor [Homo sapiens] −2.03 ACSM1 acyl-coenzyme A synthetase ACSM1, mitochondrial [Homo sapiens] −3.05 disintegrin and metalloproteinase domain-containing protein 19 preproprotein [Homo ADAM19 −1.65 sapiens] disintegrin and metalloproteinase
    [Show full text]
  • The Hypothalamus As a Hub for SARS-Cov-2 Brain Infection and Pathogenesis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.08.139329; this version posted June 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis Sreekala Nampoothiri1,2#, Florent Sauve1,2#, Gaëtan Ternier1,2ƒ, Daniela Fernandois1,2 ƒ, Caio Coelho1,2, Monica ImBernon1,2, Eleonora Deligia1,2, Romain PerBet1, Vincent Florent1,2,3, Marc Baroncini1,2, Florence Pasquier1,4, François Trottein5, Claude-Alain Maurage1,2, Virginie Mattot1,2‡, Paolo GiacoBini1,2‡, S. Rasika1,2‡*, Vincent Prevot1,2‡* 1 Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France 2 LaBoratorY of Development and PlasticitY of the Neuroendocrine Brain, FHU 1000 daYs for health, EGID, School of Medicine, Lille, France 3 Nutrition, Arras General Hospital, Arras, France 4 Centre mémoire ressources et recherche, CHU Lille, LiCEND, Lille, France 5 Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and ImmunitY of Lille (CIIL), Lille, France. # and ƒ These authors contriButed equallY to this work. ‡ These authors directed this work *Correspondence to: [email protected] and [email protected] Short title: Covid-19: the hypothalamic hypothesis 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.08.139329; this version posted June 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 As Potential Molecular Markers in Advanced Human Gastric Cancer
    Hindawi Publishing Corporation Disease Markers Volume 2014, Article ID 285906, 9 pages http://dx.doi.org/10.1155/2014/285906 Research Article Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 as Potential Molecular Markers in Advanced Human Gastric Cancer Sol de la Peña,1 Clara Luz Sampieri,2 Mariana Ochoa-Lara,3 Kenneth León-Córdoba,4 and José María Remes-Troche5 1 Biomedical Sciences Doctoral Program, Biomedical Research Center, University of Veracruz, 91190 Xalapa, Veracruz, Mexico 2 Institute of Public Health, University of Veracruz, 91190 Xalapa, Veracruz, Mexico 3 Public Health Master Program, University of Veracruz, 91190 Xalapa, Veracruz, Mexico 4 Dr. Miguel Dorantes Mesa Hospital, 91130 Xalapa, Veracruz, Mexico 5 Medical-Biological Research Institute, University of Veracruz, 91700 Veracruz, Veracruz, Mexico Correspondence should be addressed to Clara Luz Sampieri; [email protected] Received 9 February 2013; Accepted 27 November 2013; Published 11 February 2014 Academic Editor: Stamatios Theocharis Copyright © 2014 Sol de la Pena˜ et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. During progression of gastric cancer (GC), degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs): changes in the expression of these have been related to unfavorable prognosis in GC. Objective. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC. Methods. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle () values, as very high ( ≤25), high ( =26–30), moderate ( =31–35), low ( =36–39), or not detected ( =40).
    [Show full text]