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Table S3. Transcriptome analysis page 1 Table S3. Transcriptomic analysis of cultured mutant and wildtype skin fibroblast. Gene Protein name GeneCards annotation OMIM Locus Fold FDR PATIENTS CONTROLS - change (n=2) (n=4) ment apoptosis apoptosis Keratinocyte Keratinocyte inflammation differentiation Neurodevelop cell growth and growth cell FPKM [SD] FPKM [SD] genes up-regulated in patient cells ESRP1 epithelial ESRP1 is an mRNA splicing factor that regulates the *612959, the gene product is an 8:95653301 - present - 0.011 0.3547 0.0038 0.0000 0.0000 splicing formation of epithelial cell-specific isoforms. epithelial cell-type-specific splicing 95719694 absent regulatory Specifically regulates the expression of FGFR2-IIIb, regulator. Mutations in ESRP1 are protein 1 an epithelial cell-specific isoform of FGFR2. Also potentially associated with autosomal regulates the splicing of CD44, CTNND1, ENAH, recessive deafness type 109. three transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). CERS3 ceramide CERS3 is a member of the ceramide synthase family #615023, autosomal recessive 15:100913143 - present - 0.011 0.1844 0.0118 0.0000 0.0000 synthase 3 of genes. The ceramide synthase enzymes regulate congenital ichthyosis type 9, 101085200 absent sphingolipid synthesis by catalyzing the formation characterized by collodian membrane at of ceramides from sphingoid base and acyl-CoA birth, acanthosis, orthohyperkeratosis, substrates. This family member is involved in the fine erythrodermic scales, palmoplantar synthesis of ceramides with ultra-long-chain acyl- hyperlinearity. moieties (ULC-Cers), important to the epidermis in its role in creating a protective barrier from the environment. GJB6 gap junction GJB6 encodes one of the connexin proteins. #129500, autosomal dominant Clouston 13:20796109 - present - 0.011 0.3381 0.0224 0.0000 0.0000 protein beta 6 Mutations in this gene have been found in some syndrome characterized by ectodermal 20806534 absent forms of deafness and in some families with hidrotic dysplasia, dystrophy of the nails and ectodermal dysplasia. hair, onycholysis, skin hyperpigmentation, palmoplantar hyperkeratosis with reduced keratinocyte desquamation, poor dental health. KRT75 keratin 75 KRT75 plays an essential role in hair and nail #612318, Pseudofulliculitis barbae, pili 12:52801363 - present - 0.011 0.2720 0.0668 0.0000 0.0000 formation. It encodes an essential component of incarnati (ingrown hairs). 52828309 absent keratin intermediate filaments in the companion layer of the hair follicle. Table S3. Transcriptome analysis page 2 S100A8 S100 calcium S100A8 has a role in the innate immune system and *123885, the S100A8/S100A9 protein 1:153362507 - present - 0.011 3.6951 0.9620 0.0000 0.0000 binding protein the regulation of inflammatory processes and complex is upregulated in lesional 153363664 absent A8 (syn. immune response. It has a major role in the calcium psoriatic skin (PMID: 24332034). calprotectin) and zinc binding of keratinocytes. CALML5 calmodulin like CALML5 is expressed in epidermis and involved in *605183, the CALML5 protein binds 10:5540657 - present - 0.011 1.3541 0.4216 0.0000 0.0000 5 the terminal differentiation of keratinocytes. calcium and interacts with TGM3, a key 5541533 absent enzyme in terminal epidermal differentiation. HDGFP1 hepatoma- Pseudogene of unknown function no associated human disease known X:130780647 - present - 0.011 27.436 9.965 0.0000 0.0000 derived growth 130780899 absent factor pseudogene 1 RHCG Rh family C RHCG encodes a glycoprotein which functions as an 268040, associated with autosomal 15:89998679 - present - 0.011 0.2132 0.0984 0.0000 0.0000 glycoprotein electroneutral and bidirectional ammonium recessive with retino-hepato- 90039844 absent transporter; it may regulate transepithelial endocrinologic syndrome. ammonia secretion. IGFL1 IGF like family The protein encoded by IGFL1 is a member of the *610544, high expression in psoriatic 19:46732220 - present - 0.011 0.3446 0.2150 0.0000 0.0000 member 1 insulin-like growth factor family of signaling skin, involved in wound healing of the 46734500 absent molecules. skin and with psoriasis. S100A9 S100 calcium The gene product of S100A9 forms a heterodimeric *123885, the S100A8/S100A9 protein 1:153330329 - present - 0.011 6.0927 4.2793 0.0000 0.0000 binding protein complex with S100A8. complex (syn. Calprotectin) is 153333503 absent A9 upregulated in lesional psoriatic skin (PMID: 24332034). SPRR3 small proline The gene is involved in keratinization. *182271, the gene product is a 1:152974222 - present - 0.011 0.2092 0.1615 0.0000 0.0000 rich protein 3 component of the cornified cell 152976332 absent envelope, which provides the protective barrier function of stratified squamous epithelial cells. KRTDAP keratinocyte KRTDAP may act as a soluble regulator of *617212, this gene encodes a protein, 19:35978225 - present - 0.011 5.3045 4.8832 0.0000 0.0000 differentiation keratinocyte differentiation. May play an important which may function in the regulation of 35986460 absent associated role in embryonic skin morphogenesis. keratinocyte differentiation and protein maintenance of stratified epithelia. SPRR2A small proline SPRR2A is a keratinocyte protein that first appears *182267, proteins of the SPRR family, 1:153028588 - present - 0.011 0.4030 0.4208 0.0000 0.0000 rich protein 2A in the cell cytosol, but ultimately becomes cross- like SPRR2A, are components of the 153030013 absent linked to membrane proteins by transglutaminase, cornified cell envelope, which provides resulting in the formation of an insoluble envelope the protective barrier function of beneath the plasma membrane. stratified squamous epithelial cells. CRCT1 cysteine rich C- no annotation *617426, the protein is the central part 1:152486977 - present - 0.011 1.3892 1.4813 0.0000 0.0000 terminal 1 of the epidermal differentiation 152488486 absent complex (EDC) (PMID: 11230159). KLK11 kallikrein The gene product of KLK11 is a serine protease *604434, the encoded protein belongs 19:51525471 - present - 0.011 0.4890 0.5342 0.0000 0.0000 related involved in collagen chain trimerization. to the kallikrein subfamily of serine 51531295 absent peptidase 11 proteases, highly expressed in fetal skin. Table S3. Transcriptome analysis page 3 LINC00473 long intergenic non-coding RNA of unknown function 6:165740775 - present - 0.043 0.2166 0.2729 0.0000 0.0000 non-protein 166401536 absent coding RNA 473 LCE3E late cornified LCE3E is involved in keratinization as a precursor of *612617, LCE3E was upregulated in 1:152538129 - present - 0.018 0.2456 0.3473 0.0000 0.0000 envelope 3E the cornified envelope of the stratum corneum. cultured normal human keratinocytes 152539248 absent by ultraviolet radiation. RP11- Transcript of unknown function Transcript of unknown function 3:125677398 - present - 0.018 0.6363 0.8999 0.0000 0.0000 666A20.3 125677660 absent SPRR4 small proline SPRR4 is involved in the cross-linked envelope *616363, SPRR proteins, such as SPRR4, 1:152943141 - present - 0.011 0.4901 0.6931 0.0000 0.0000 rich protein 4 protein of keratinocytes and in UV-induced are precursors for the cornified cell 152945050 absent cornification. envelope, a structure formed in the outermost layers of stratified squamous epithelia. Cabral et al. (2001) concluded that SPRR4 is not expressed in skin under normal conditions, but is rather highly induced after UV irradiation and selectively incorporated into immature, fragile, and poorly hydrophobic cell envelopes. They hypothesized that SPRR4 is involved in maintenance of skin integrity following UV exposure (PMID: 11719550). AC092580. LincRNA Transcript of unknown function Transcript of unknown function 2:7811734 - absent - 0.018 0.0000 0.0000 0.1602 0.0615 3 7812377 present KRT5 keratin 5 KRT5 is a type II cytokeratin which is specifically #179850, #131760, autosomal dominant 12:52840434 - 111.59 0.011 33.887 5.9874 0.3037 0.7667 expressed in the basal layer of the epidermis with Dermatopathia pigmentosa reticularis 53012343 family member KRT14. It is involved with and Epidermolysis bullosa simplex, keratinization. which is characterized by recurrent blistering of the skin after minor physical trauma as a result of cytolysis within basal epidermal cells. It is often associated with hyperkeratosis of the palms and soles, and shows clumping of keratin filaments in basal epidermal cells. SOX2-OT SOX2 non-coding RNA of unknown function non-coding RNA of unknown function 3:180701496 - 91.05 0.011 10.225 14.419 0.1123 0.1345 overlapping 181554668 transcript Table S3. Transcriptome analysis page 4 KRT14 keratin 14 KRT14 is a type I cytokeratin which is specifically #125595, #131760, autosomal dominant 17:39738530 - 78.55 0.025 17.975 1.557 0.2288 0.4008 expressed in the basal layer of the epidermis with Dermatopathia pigmentosa reticularis 39743173 family member KRT5. It is involved with and Epidermolysis bullosa simplex, keratinization. which is characterized by localized blistering of the skin and absence of dermatoglyphics (fingerprint lines), thickening of the palms and soles (palmo-plantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. CDH1 cadherin 1 Cadherins are calcium-dependent cell adhesion #119580, Blepharocheilodontic 16:68771127 - 52.69 0.011 0.8382 0.0061 0.0159 0.0414 proteins. CDH1 is involved in mechanisms regulating syndrome is a rare autosomal dominant 68869451 cell-cell adhesions, mobility and proliferation
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    Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia.
  • Podocalyxin Is Required for Maintaining Blood–Brain Barrier Function During Acute Inflammation

    Podocalyxin Is Required for Maintaining Blood–Brain Barrier Function During Acute Inflammation

    Podocalyxin is required for maintaining blood–brain barrier function during acute inflammation Jessica Caita, Michael R. Hughesa,1, Matthew R. Zeglinskib,c,d, Allen W. Chane,f,g,h,i, Sabrina Osterhofa, R. Wilder Scotta,j, Diana Canals Hernaeza, Alissa Caita, A. Wayne Voglj,k, Pascal Bernatchezd,l, T. Michael Underhilla,j, David J. Granvilleb,c,d, Timothy H. Murphye,f,g, Calvin D. Roskelleyj,k, and Kelly M. McNagnya,1 aBiomedical Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; bICORD Centre, University of British Columbia, Vancouver, BC, Canada V5Z 1M9; cDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada V6T 2B5; dCentre for Heart and Lung Innovation, St Paul’s Hospital, Vancouver, BC, Canada V6Z 1Y6; eDepartment of Psychiatry, University of British Columbia, Vancouver, BC, Canada V6T 2A1; fKinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z4; gDjavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; hNeuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada T6G 2R3; iNeurochemical Research Unit, Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2R3; jDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z4; kLife Sciences Institute, University of British Columbia, Vancouver, BC, Canada V6T 1Z4; and lDepartment of Anaesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved January 15, 2019 (received for review September 6, 2018) Podocalyxin (Podxl) is broadly expressed on the luminal face of and plasma factors to effect repair.