DOCSLIB.ORG

The Effect of Type 2 Diabetes Mellitus and Obesity on Muscle Progenitor Cell Function Shuzhi Teng* and Ping Huang*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effect of Type 2 Diabetes Mellitus and Obesity on Muscle Progenitor Cell Function Shuzhi Teng* and Ping Huang* Teng and Huang Stem Cell Research & Therapy (2019) 10:103 https://doi.org/10.1186/s13287-019-1186-0 REVIEW Open Access The effect of type 2 diabetes mellitus and obesity on muscle progenitor cell function Shuzhi Teng* and Ping Huang* Abstract In addition to its primary function to provide movement and maintain posture, the skeletal muscle plays important roles in energy and glucose metabolism. In healthy humans, skeletal muscle is the major site for postprandial glucose uptake and impairment of this process contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). A key component to the maintenance of skeletal muscle integrity and plasticity is the presence of muscle progenitor cells, including satellite cells, fibroadipogenic progenitors, and some interstitial progenitor cells associated with vessels (myo-endothelial cells, pericytes, and mesoangioblasts). In this review, we aim to discuss the emerging concepts related to these progenitor cells, focusing on the identification and characterization of distinct progenitor cell populations, and the impact of obesity and T2DM on these cells. The recent advances in stem cell therapies by targeting diabetic and obese muscle are also discussed. Keywords: Satellite cell, muscle progenitor cell, T2DM, Obesity Background A major metabolic defect associated with T2DM is the The incidence of overweight has been increasing dramatic- failure of proper glucose utilization by peripheral tissues ally worldwide due to increased uptake of high-calorie food, such as skeletal muscle and adipose tissue, the primary lack of physical activity, and genetic predisposition. Accord- targets of insulin-stimulated glucose uptake. In healthy ingly, obesity and its associated metabolic diseases such as humans, 70–80% of glucose uptake occurs in skeletal type 2 diabetes mellitus (T2DM) have become an epidemic muscle in the postprandial state through both health threat and economic burden [1]. According to a re- insulin-dependent phosphoinositide-3-kinase-protein kin- cent study, by 2025, global obesity prevalence is expected ase B (PI3K-PKB/AKT) pathway and insulin-independent to reach 18% in men and surpass 21% in women [2]. From glucose-stimulated Baf60c-Deptor-AKT pathway [5, 6]. 1980 to 2014, global age-standardized diabetes prevalence Moreover, studies of genetically predisposed individuals increased from 4.3 to 9.0% in men and from 5.0 to 7.9% in indicate that insulin resistance in muscle is the primary or women [3]. Both genetic and environmental factors play initiating defect leading to the ultimate development of pivotal roles in the pathogenesis of T2DM, among them T2DM [7, 8]. Skeletal muscle not only plays an important obesity is a major risk factor—around 50% of obese subjects role in the pathogenesis of T2DM but also undergoes sig- will develop T2DM at some stage [4]. While insulin resist- nificant structural, metabolic, and functional changes ance in peripheral tissues is often an early sign of develop- under obese and diabetic conditions, such as muscle atro- ing diabetes, pancreatic β cell function is damaged phy [9, 10], fiber-type transition [11], impaired glucose up- gradually during disease progression. Over time chronic take [12], glycogen synthesis [13, 14], fatty acid oxidation hyperglycemia and hyperlipidemia impair cellular functions, [15], and altered myokine secretion [16, 17], which ultim- which eventually lead to various complications including ately lead to muscle weakness and poor exercise diabetic retinopathy, nephropathy, neuropathy, diabetic performance. foot, and cardiovascular diseases [4]. Many of the morphological features of muscle atrophy resemble those seen in sarcopenia, an age-associated loss * Correspondence: [email protected]; [email protected] of skeletal muscle mass and function [18]. Both muscle Shuzhi Teng and Ping Huang are co-corresponding authors. The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune atrophy and sarcopenia are characterized by a decrease College of Medicine, Jilin University, 126 Xinmin Street, Changchun, Jilin in myofiber size and muscle mass, and the ensuing loss 130021, People’s Republic of China © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Teng and Huang Stem Cell Research & Therapy (2019) 10:103 Page 2 of 15 of muscle strength. Loss of appendicular lean mass and serves as a major contributor to the postnatal muscle reduced skeletal muscle strength are commonly ob- growth and repair after injury or disease [38, 39]. In adult- served in T2DM patients despite gender and ethnicity hood, satellite cells remain quiescent under normal condi- and the incidence increases with aging [19, 20]. It is esti- tions. Upon injury or in diseased states, satellite cells are mated that sarcopenia is present in about 5 to 10 % of reactivated, proliferating to generate a pool of myoblasts, persons over 65 years of age [21], whereas the T2DM which then differentiate and fuse with damaged fibers or patients have two to three times higher prevalence of fuse with each other to generate entirely new myofibers. sarcopenia than non-diabetic individuals [22, 23] due to Meanwhile, some myoblasts remain undifferentiated and glucose toxicity, insulin resistance, and oxidative stress return to the quiescent state to replenish the satellite cell [21]. In addition, intermuscular adipose tissue infiltration pool. During muscle development and regeneration, myo- is increased in persons with obesity, diabetes, and per- genic regulatory factors (MRFs) Myf5, MyoD, MRF4, and ipheral neuropathy [24]. This ectopic fat accumulation is myogenin are activated for entry of satellite cells into the associated with impaired muscle function and forms the myogenic program [40]. The importance of satellite cells basis of obese sarcopenia [24]. for muscle regeneration is reinforced by genetic ablation A key component to the maintenance of skeletal of Pax7 expressing cells after acute injury. Lepper and muscle integrity and plasticity is the presence of muscle colleagues found that such elimination completely blocked progenitor cells, including satellite cells, fibroadipogenic muscle regeneration, thus verified that satellite cells, as progenitors, myo-endothelial cells, and other interstitial adult stem cells, are indispensable for acute injury-in- progenitor cells [25–29]. These heterogenous groups of duced muscle regeneration [39]. cells are endowed with multilineage developmental po- tential and may contribute to the pathogenesis as well as the treatment of muscle diseases. The proliferation and differentiation of satellite cells are Accumulating evidence indicates that diabetic and attenuated in diabetic muscles obese conditions not only cause dramatic structural, The impairment of muscle regeneration was observed in metabolic and functional changes of skeletal muscle fi- animal studies under hyperglycemia and/or lipotoxicity bers but also display detrimental effects on these pro- conditions, but the detailed changes especially alter- genitor cells [30, 31]. Therefore, fully characterization of ations of satellite cells vary from study to study, and distinct progenitor cell populations and understanding some results are even conflicting (Table 1). Using a the impact of aging, obesity, and T2DM on these cells mouse model of insulin resistance achieved by high-fat will aid to extend our understanding of these health con- diet (HFD) feeding for 8 months, Hu et al. observed ditions and shed light on developing novel therapeutic smaller regenerating myofibers plus more collagen de- interventions. position after cardiotoxin injury [30]. However, satellite cell activation or proliferation was intact as assessed by Effect of T2DM and obesity on skeletal muscle bromodeoxyuridine (BrdU; an analog of the nucleoside stem cell—satellite cell thymidine) incorporation and by the expression of myo- Satellite cell discovery and function genic transcription factors. Instead, the deficits in muscle The satellite cell was first identified by transmission regeneration were principally related to increased ex- electron microscopy on frog muscle and named after its pression of phosphatase and tensin homolog (PTEN), anatomical localization: mononuclear cell wedged be- which reduced phosphatidylinositol (3,4,5)-trisphosphate tween basal lamina and the plasma membrane of myofi- (PIP3) in muscle, inhibited AKT signaling, and impaired ber, like a “satellite” cell “orbiting” the muscle fiber when myofiber maturation [30]. viewed in cross-section [25]. Shortly afterwards, the sat- On the other hand, HFD-feeding 3-week-old mice for ellite cell was found in other vertebrates including hu- just 3 weeks resulted in overweight, decreased satellite cell man [32]. Subsequent studies proved that satellite cells content and muscle mass, and reduced regenerative cap- are capable of proliferation and myogenic differentiation ability [41]. In another study, HFD-feeding 4-week-old in vitro and in vivo [33, 34]. Recent studies further
Load more

Recommended publications
  • Gluteal Muscle Contracture: Diagnosis and Management Options
    SICOT J 2017, 3,1 Ó The Authors, published by EDP Sciences, 2017 DOI: 10.1051/sicotj/2016036 Available online at: www.sicot-j.org REVIEW ARTICLE OPEN ACCESS Gluteal muscle contracture: diagnosis and management options Saroj Rai1, Chunqing Meng1,*, Xiaohong Wang1, Nabin Chaudhary2, Shengyang Jin1, Shuhua Yang1, and Hong Wang1 1 Department of Orthopedics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, #1277 Jiefang Avenue, 430022 Wuhan, P.R. China 2 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, #1095 Jiefang Avenue, 430030 Wuhan, P.R. China Received 14 April 2016, Accepted 29 October 2016, Published online 6 January 2017 Abstract – Gluteal muscle contracture (GMC), a debilitating disease, exists all over the globe but it is much more prevalent in China. Patients typically present with abduction and external rotation of the hip and are unable to bring both the knees together while squatting. Multiple etiologies have been postulated, the commonest being repeated intramuscular injection into the buttocks. The disease is diagnosed primarily by clinical features but radiological features are necessary for the exclusion of other pathological conditions. Non-operative treatment with physiotherapy can be tried before surgery is considered but it usually fails. Different surgical techniques have been described and claimed to have a better outcome of one over another but controversy still exists. Based on published literatures, the clinical outcome is exceptionally good in all established methods of surgery. However, endoscopic surgery is superior to conventional open surgery in terms of cosmetic outcome with fewer complications. Nevertheless, its use has been limited by lack of adequate knowledge, instrumentations, and some inherent limitations.
    [Show full text]
  • Structure of Protein Related to Dan and Cerberus: Insights Into the Mechanism of Bone Morphogenetic Protein Antagonism
    Structure Article Structure of Protein Related to Dan and Cerberus: Insights into the Mechanism of Bone Morphogenetic Protein Antagonism Kristof Nolan,1,5 Chandramohan Kattamuri,1,5 David M. Luedeke,1 Xiaodi Deng,1 Amrita Jagpal,2 Fuming Zhang,3 Robert J. Linhardt,3,4 Alan P. Kenny,2 Aaron M. Zorn,2 and Thomas B. Thompson1,* 1Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Medical Sciences Building, Cincinnati, OH 45267, USA 2Perinatal Institute, Cincinnati Children’s Research Foundation and Department of Pediatrics, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA 3Departments of Chemical and Biological Engineering and Chemistry and Chemical Biology 4Departments of Biology and Biomedical Engineering Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA 5These authors contributed equally to this work *Correspondence: [email protected] http://dx.doi.org/10.1016/j.str.2013.06.005 SUMMARY follicular development, as well as gut differentiation from meso- derm tissue (Bragdon et al., 2011). Furthermore, their roles in The bone morphogenetic proteins (BMPs) are several disease states, including lung and kidney fibrosis, oste- secreted ligands largely known for their functional oporosis, and cardiovascular disease, have indicated their roles in embryogenesis and tissue development. A importance in adult homeostasis (Cai et al., 2012; Walsh et al., number of structurally diverse extracellular antago- 2010). nists inhibit BMP ligands to regulate signaling. The At the molecular level, BMP ligands form stable disulfide- differential screening-selected gene aberrative in bonded dimers that transduce their signals by binding two type I and two type II receptors, leading to type I receptor phos- neuroblastoma (DAN) family of antagonists repre- phorylation.
    [Show full text]
  • Cancer Cachexia Decreases Specific Force and Accelerates Fatigue in Limb Muscle
    Biochemical and Biophysical Research Communications 435 (2013) 488–492 Contents lists available at SciVerse ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc Cancer cachexia decreases specific force and accelerates fatigue in limb muscle ⇑ B.M. Roberts a, G.S. Frye b, B. Ahn b, L.F. Ferreira b,1, A.R. Judge a,1, a 1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA b 1864 Stadium Road, Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL 32610, USA article info abstract Article history: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle Received 30 April 2013 mass and weakness, which compromises physical function, reduces quality of life, and ultimately can Available online 11 May 2013 lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atro- phy and consequent decline in muscle force generating capacity. However, more recently, we provided Keywords: evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be Muscle weakness entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a conse- Muscle atrophy quence of muscle atrophy but that there is also significant contractile dysfunction. The current study C-26 aimed to determine whether contractile dysfunction is also present in limb muscles during severe Contractile dysfunction Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the dia- phragm.
    [Show full text]
  • Mice Subjected to Ap2-Cre Mediated Ablation of Microsomal Triglyceride Transfer Protein Are Resistant to High Fat Diet Induced Obesity Ahmed Bakillah1,2* and M
    Bakillah and Hussain Nutrition & Metabolism (2016) 13:1 DOI 10.1186/s12986-016-0061-6 RESEARCH Open Access Mice subjected to aP2-Cre mediated ablation of microsomal triglyceride transfer protein are resistant to high fat diet induced obesity Ahmed Bakillah1,2* and M. Mahmood Hussain1,2,3 Abstract Background: Microsomal triglyceride transfer protein (MTP) is essential for the assembly of lipoproteins. MTP has been shown on the surface of lipid droplets of adipocytes; however its function in adipose tissue is not well defined. We hypothesized that MTP may play critical role in adipose lipid droplet formation and expansion. Methods: Plasmids mediated overexpression and siRNA mediated knockdown of Mttp gene were performed in 3T3-L1 pre-adipocytes to evaluate the effects of MTP on cell differentiation and triglyceride accumulation. Adipose- specific knockdown of MTP was achieved in mice bybreeding MTP floxed (Mttpfl/fl) mice with aP2-Cre recombinase transgenic mice. Adipose-specific MTP deficient (A-Mttp-/-) mice were fed 60 % high-fat diet (HFD), and the effects of MTP knockdown on body weight, body fat composition, plasma and tissues lipid composition, glucose metabolism, lipogenesis and intestinal absorption was studied. Lipids were measured in total fasting plasma and size fractionated plasma using colorimetric assays. Gene expression was investigated by Real-Time quantitative PCR. All data was assessed using t-test, ANOVA. Results: MTP expression increased during early differentiation in 3T3-L1 cells, and declined later. The increases in MTP expression preceded PPARγ expression. MTP overexpression enhanced lipid droplets formation, and knockdown attenuated cellular lipid accumulation. These studies indicated that MTP positively affects adipogenesis.
    [Show full text]
  • The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations
    THE MEDICAL MANAGEMENT OF FIBRODYSPLASIA OSSIFICANS PROGRESSIVA: CURRENT TREATMENT CONSIDERATIONS The International Clinical Consortium on Fibrodysplasia Ossificans Progressiva1 May 2011 From The Center for Research in FOP and Related Disorders, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104 Corresponding Editor: Frederick S. Kaplan, M.D. Isaac and Rose Nassau Professor of Orthopaedic Molecular Medicine Director, Center for Research in FOP & Related Disorders The Perelman School of Medicine - The University of Pennsylvania Department of Orthopaedic Surgery 3737 Market Street – Sixth Floor Philadelphia, PA 19104, USA Tel: (office) 215-294-9145 Fax: 215-222-8854 Email: [email protected] Reprint Requests: [email protected] Associate Editors: Eileen M. Shore, Ph.D. Robert J. Pignolo, M.D., Ph.D. [Kaplan FS, Shore EM, Pignolo RJ (eds), name of individual consortium member, and The International Clinical Consortium on FOP. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP 4:1-100, 2011] 1See Section X (pages 84-100) for Complete Author Listing. ` 1 ABSTRACT…………………………………………………………………………………………… 5 I. THE CLINICAL AND BASIC SCIENCE BACKGROUND OF FOP……………..…………….. 6 A. Introduction………………………………………………………………..…..…..…………………. 6 B. Classic Clinical Features of FOP……………………………………………………..……………. 6 C. Other Skeletal Anomalies in FOP…………………………………………………………… 6 D. Radiographic Features of FOP……………………………………………………….…….... 7 E. Histopathology of FOP Lesions………………………………………………………………. 7 F. Laboratory Findings in FOP………………………………………………………………… 8 G. The Immune System & FOP…………………………………………………………………. 8 H. Misdiagnosis of FOP………………………………………………………………………………… 8 I. Epidemiologic, Genetic & Environmental Factors in FOP……………………..…………. 9 J. FOP & the BMP Signaling Pathway………………………………………………………… 9 K. The FOP Gene………………………………………………………………..………………. 9 L. Structural and Functional Consequences of the FOP Mutation…………………………… 10 M.
    [Show full text]
  • Spinal and Bulbar Muscular Atrophy
    Spinal and bulbar muscular atrophy Description Spinal and bulbar muscular atrophy, also known as Kennedy disease, is a disorder of specialized nerve cells that control muscle movement (motor neurons). These nerve cells originate in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). Spinal and bulbar muscular atrophy mainly affects males and is characterized by muscle weakness and wasting (atrophy) that usually begins in adulthood and worsens slowly over time. Muscle wasting in the arms and legs results in cramping; leg muscle weakness can also lead to difficulty walking and a tendency to fall. Certain muscles in the face and throat (bulbar muscles) are also affected, which causes progressive problems with swallowing and speech. Additionally, muscle twitches (fasciculations) are common. Some males with the disorder experience unusual breast development ( gynecomastia) and may be unable to father a child (infertile). Frequency This condition affects fewer than 1 in 150,000 males and is very rare in females. Causes Spinal and bulbar muscular atrophy results from a particular type of mutation in the AR gene. This gene provides instructions for making a protein called an androgen receptor. This receptor attaches (binds) to a class of hormones called androgens, which are involved in male sexual development. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive. The AR gene mutation that causes spinal and bulbar muscular atrophy is the abnormal expansion of a DNA segment called a CAG triplet repeat. Normally, this DNA segment is repeated up to about 36 times.
    [Show full text]
  • Cachexia Signaling-A Targeted Approach to Cancer Treatment
    Author Manuscript Published OnlineFirst on June 23, 2016; DOI: 10.1158/1078-0432.CCR-16-0495 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Molecular Pathways: Cachexia Signaling—A Targeted Approach to Cancer Treatment Yuji Miyamoto1, Diana L. Hanna1, Wu Zhang1, Hideo Baba2, and Heinz-Josef Lenz1 1Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California. 2Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. Corresponding Author: Heinz-Josef Lenz, Division of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033. Phone: 323-865-3967; Fax: 323-865-0061; E-mail: [email protected] Grant Support H.-J. Lenz was supported by the NIH under award number P30CA014089, Wunder Project, Call to Cure, and Danny Butler Memorial Fund. Disclosure of Potential Conflicts of Interest H.-J. Lenz is a consultant/advisory board member for Bayer, Boehringer Ingelheim, Celgene, Merck Serono, and Roche. No other potential conflicts of interest were disclosed. Running Title: A Targeted Approach to Cancer Treatment Downloaded from clincancerres.aacrjournals.org on September 28, 2021. © 2016 American Association for Cancer Research. Author Manuscript Published OnlineFirst on June 23, 2016; DOI: 10.1158/1078-0432.CCR-16-0495 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Abstract Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively impacts quality of life and portends a poor prognosis.
    [Show full text]
  • A Acanthosis Nigricans, 139 Acquired Ichthyosis, 53, 126, 127, 159 Acute
    Index A Anti-EJ, 213, 214, 216 Acanthosis nigricans, 139 Anti-Ferc, 217 Acquired ichthyosis, 53, 126, 127, 159 Antigliadin antibodies, 336 Acute interstitial pneumonia (AIP), 79, 81 Antihistamines, 324 Adenocarcinoma, 115, 116, 151, 173 Anti-histidyl-tRNA-synthetase antibody Adenosine triphosphate (ATP), 229 (Anti-Jo-1), 6, 14, 140, 166, 183, Adhesion molecules, 225–226 213–216 Adrenal gland carcinoma, 115 Anti-histone antibodies (AHA), 174, 217 Age, 30–32, 157–159 Anti-Jo-1 antibody syndrome, 34, 129 Alanine aminotransferase (ALT, ALAT), 16, Anti-Ki-67 antibody, 247 128, 205, 207, 255 Anti-KJ antibodies, 216–217 Alanyl-tRNA synthetase, 216 Anti-KS, 82 Aldolase, 14, 16, 128, 129, 205, 207, 255, 257 Anti-Ku antibodies, 163, 165, 217 Aledronate, 325 Anti-Mas, 217 Algorithm, 256, 259 Anti-Mi-2 Allergic contact dermatitis, 261 antibody syndrome, 11, 129, 215 Alopecia, 62, 199, 290 antibodies, 6, 15, 129, 142, 212 Aluminum hydroxide, 325, 326 Anti-Myo 22/25 antibodies, 217 Alzheimer’s disease-related proteins, 190 Anti-Myosin scintigraphy, 230 Aminoacyl-tRNA synthetases, 151, 166, 182, Antineoplastic agents, 172 212, 215 Antineoplastic medicines, 169 Aminoquinolone antimalarials, 309–310, 323 Antinuclear antibody (ANA), 1, 141, 152, 171, Amyloid, 188–190 172, 174, 213, 217 Amyopathic DM, 6, 9, 29–30, 32–33, 36, 104, Anti-OJ, 213–214, 216 116, 117, 147–153 Anti-p155, 214–215 Amyotrophic lateral sclerosis, 263 Antiphospholipid syndrome (APS), 127, Antisynthetase syndrome, 11, 33–34, 81 130, 219 Anaphylaxi, 316 Anti-PL-7 antibody, 82, 214 Anasarca,
    [Show full text]
  • Muscle Biopsy Features of Idiopathic Inflammatory Myopathies And
    Autoimmun Highlights (2014) 5:77–85 DOI 10.1007/s13317-014-0062-2 REVIEW ARTICLE Muscle biopsy features of idiopathic inflammatory myopathies and differential diagnosis Gaetano Vattemi • Massimiliano Mirabella • Valeria Guglielmi • Matteo Lucchini • Giuliano Tomelleri • Anna Ghirardello • Andrea Doria Received: 1 August 2014 / Accepted: 22 August 2014 / Published online: 10 September 2014 Ó Springer International Publishing Switzerland 2014 Abstract The gold standard to characterize idiopathic Keywords Inflammatory myopathy Á Autoimmune inflammatory myopathies is the morphological, immuno- myositis Á Histopathology Á Differential diagnosis histochemical and immunopathological analysis of muscle biopsy. Mononuclear cell infiltrates and muscle fiber necrosis are commonly shared histopathological features. Introduction Inflammatory cells that surround, invade and destroy healthy muscle fibers expressing MHC class I antigen are Idiopathic inflammatory myopathies (IIM) are a heteroge- the typical pathological finding of polymyositis. Perifas- neous group of acquired muscle diseases, which have dis- cicular atrophy and microangiopathy strongly support a tinct clinical, pathological and histological features [1, 2]. diagnosis of dermatomyositis. Randomly distributed The most common IIM seen in clinical practice can be necrotic muscle fibers without mononuclear cell infiltrates separated into four categories including polymyositis (PM), represent the histopathological hallmark of immune-med- dermatomyositis (DM), immune-mediated necrotizing iated necrotizing myopathy; meanwhile, endomysial myopathy (NM) and sporadic inclusion body myositis inflammation and muscle fiber degeneration are the two (sIBM) [1, 3]. main pathological features in sporadic inclusion body In the diagnostic workup of an inflammatory myopathy, myositis. A correct differential diagnosis requires immu- muscle biopsy is an indispensable and sensitive tool for nopathological analysis of the muscle biopsy and has establishing the diagnosis.
    [Show full text]
  • ACVR1, a Therapeutic Target of Fibrodysplasia Ossificans Progressiva, Is Negatively Regulated by Mir-148A
    Int. J. Mol. Sci. 2012, 13, 2063-2077; doi:10.3390/ijms13022063 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article ACVR1, a Therapeutic Target of Fibrodysplasia Ossificans Progressiva, Is Negatively Regulated by miR-148a Hao Song 1,2,†, Qi Wang 1,†, Junge Wen 2, Shunai Liu 1, Xuesong Gao 1, Jun Cheng 1,* and Deli Zhang 2,* 1 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; E-Mails: [email protected] (H.S.); [email protected] (Q.W.); [email protected] (S.L.); [email protected] (X.G.) 2 Research Laboratory of Virology, Immunology & Bioinformatics, Northwest A & F University, Xianyang 712100, Shaanxi, China; E-Mail: [email protected] † These authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: [email protected] (J.C.); [email protected] (D.Z.); Tel.: +86-10-84322006 (J.C.); Fax: +86-10-84397196 (J.C.); Tel./Fax: +86-029-87092120 (D.Z.). Received: 4 November 2011; in revised form: 3 February 2012 / Accepted: 7 February 2012 / Published: 15 February 2012 Abstract: Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of skeletal malformations and progressive extraskeletal ossification. There is still no effective treatment for FOP. All FOP individuals harbor conserved point mutations in ACVR1 gene that are thought to cause ACVR1 constitutive activation and activate BMP signal pathway. The constitutively active ACVR1 is also found to be able to cause endothelial-to-mesenchymal transition (EndMT) in endothelial cells, which may cause the formation of FOP lesions.
    [Show full text]
  • Spinal Muscular Atrophy
    FACT SHEET SPINAL MUSCULAR ATROPHY Spinal Muscular Atrophy (SMA) is a Motor Neuron Disease. It is caused by the mutation of the Survival of SYMPTOMS IN INFANTS • Muscle weakness. Motor Neuron (SMN) gene. It occurs due to the loss of • Muscle atrophy (wasting). motor neurons within the spinal cord and brain. It results • Poor muscle tone. in the progressive wasting away of muscles (atrophy) and • Areflexia (delayed reflexes). muscle weakness. SMA can affect people of all ages, races • Weak cry. or genders; however, the majority of cases occur in infancy • Difficulty sucking or swallowing. or childhood. There are four types of SMA. • Feeding difficulties. FORMS OF SMA • Weak cough. • Lack of developmental milestones (inability to lift head TYPE I (ACUTE INFANTILE) or sit up). • Also called Wernig-Hoffman Disease. • Limpness or a tendency to flop. • Most severe form of SMA. • Accumulations of secretions in the lungs or throat. • Usually diagnosed before six months of age. • Those affected cannot sit without support, lungs may SYMPTOMS IN ADULTS not fully develop, swallowing and breathing may be • Muscle weakness. difficult and there is weakness of the intercostal muscles • Muscle atrophy (wasting). (muscles between the ribs). • Weak tongue. • 95 per cent fatal by 18 • Stiffness. • Cramps. TYPE II (CHRONIC INFANTILE) • Fasciculation (twitching). • Usually diagnosed before the age of two, with the • Clumsiness. majority of cases diagnosed by 15 months. • Dyspnea (shortness of breath). • May be able to sit without assistance or even stand with support. DIAGNOSIS • Increased risk for complications from respiratory • A diagnosis can be made by an SMN gene test which infections.
    [Show full text]
  • Skeletal Muscle Damage in COVID-19: a Call for Action
    medicina Review Skeletal Muscle Damage in COVID-19: A Call for Action Amira Mohammed Ali 1,2,* and Hiroshi Kunugi 3,4 1 Department of Psychiatric Nursing and Mental Health, Faculty of Nursing, Alexandria University, Alexandria 21527, Egypt 2 Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan 3 Department of Psychiatry, School of Medicine, Teikyo University, Tokyo 173-8605, Japan; [email protected] 4 Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan * Correspondence: [email protected]; Tel.: +81-042-346-1986 Abstract: Both laboratory investigations and body composition quantification measures (e.g., com- puted tomography, CT) portray muscle loss in symptomatic Coronavirus disease 2019 (COVID-19) patients. Muscle loss is associated with a poor prognosis of the disease. The exact mechanism of muscle damage in COVID-19 patients, as well as the long-term consequences of muscle injury in disease survivors, are unclear. The current review briefly summarizes the literature for mechanisms, assessment measures, and interventions relevant to skeletal muscle insult in COVID-19 patients. Muscle injury is likely to be attributed to the cytokine storm, disease severity, malnutrition, prolonged physical inactivity during intensive care unit (ICU) stays, mechanical ventilation, and myotoxic drugs (e.g., dexamethasone). It has been assessed by imaging and non-imaging techniques (e.g., CT and electromyography), physical performance tests (e.g., six-minute walk test), anthropometric measures (e.g., calf circumference), and biomarkers of muscle dystrophy (e.g., creatine kinase). Interventions Citation: Ali, A.M.; Kunugi, H.
    [Show full text]