{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:36:29Z","timestamp":1784140589583,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014857","name":"National Natural Science Foundation of China-Guangdong Joint Fund","doi-asserted-by":"publisher","award":["2019A1515010923"],"award-info":[{"award-number":["2019A1515010923"]}],"id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Transmembrane proteins are vital for intercellular signalling and play important roles in the control of cell fate. However, their physiological functions and mechanisms of action in myogenesis and muscle disorders remain largely unexplored. It has been found that <jats:italic>transmembrane protein 182<\/jats:italic> (<jats:italic>TMEM182<\/jats:italic>) is dramatically up\u2010regulated during myogenesis, but its detailed functions remain unclear. This study aimed to analyse the function of <jats:italic>TMEM182<\/jats:italic> during myogenesis and muscle regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA sequencing, quantitative real\u2010time polymerase chain reaction, and immunofluorescence approaches were used to analyse <jats:italic>TMEM182<\/jats:italic> expression during myoblast differentiation. A dual\u2010luciferase reporter assay was used to identify the promoter region of the <jats:italic>TMEM182<\/jats:italic> gene, and a chromatin immunoprecipitation assay was used to investigate the regulation <jats:italic>TMEM182<\/jats:italic> transcription by MyoD. We used chickens and <jats:italic>TMEM182<\/jats:italic>\u2010knockout mice as <jats:italic>in vivo<\/jats:italic> models to examine the function of <jats:italic>TMEM182<\/jats:italic> in muscle growth and muscle regeneration. Chickens and mouse primary myoblasts were used to extend the findings to <jats:italic>in vitro<\/jats:italic> effects on myoblast differentiation and fusion. Co\u2010immunoprecipitation and mass spectrometry were used to identify the interaction between <jats:italic>TMEM182<\/jats:italic> and integrin beta 1 (ITGB1). The molecular mechanism by which <jats:italic>TMEM182<\/jats:italic> regulates myogenesis and muscle regeneration was examined by Transwell migration, cell wound healing, adhesion, glutathione\u2010S\u2010transferse pull down, protein purification, and RNA immunoprecipitation assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>TMEM182<\/jats:italic> was specifically expressed in skeletal muscle and adipose tissue and was regulated at the transcriptional level by the myogenic regulatory factor MyoD1. Functionally, <jats:italic>TMEM182<\/jats:italic> inhibited myoblast differentiation and fusion. The <jats:italic>in vivo<\/jats:italic> studies indicated that <jats:italic>TMEM182<\/jats:italic> induced muscle fibre atrophy and delayed muscle regeneration. <jats:italic>TMEM182<\/jats:italic> knockout in mice led to significant increases in body weight, muscle mass, muscle fibre number, and muscle fibre diameter. Skeletal muscle regeneration was accelerated in <jats:italic>TMEM182<\/jats:italic>\u2010knockout mice. Furthermore, we revealed that the inhibitory roles of <jats:italic>TMEM182<\/jats:italic> in skeletal muscle depend on ITGB1, an essential membrane receptor involved in cell adhesion and muscle formation. <jats:italic>TMEM182<\/jats:italic> directly interacted with ITGB1, and this interaction required an extracellular hybrid domain of ITGB1 (aa 387\u2013470) and a conserved region (aa 52\u201362) within the large extracellular loop of <jats:italic>TMEM182<\/jats:italic>. Mechanistically, <jats:italic>TMEM182<\/jats:italic> modulated ITGB1 activation by coordinating the association between ITGB1 and laminin and regulating the intracellular signalling of ITGB1. Myogenic deletion of <jats:italic>TMEM182<\/jats:italic> increased the binding activity of ITGB1 to laminin and induced the activation of the FAK\u2010ERK and FAK\u2010Akt signalling axes during myogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data reveal that <jats:italic>TMEM182<\/jats:italic> is a novel negative regulator of myogenic differentiation and muscle regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12767","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T04:46:31Z","timestamp":1629780391000},"page":"1704-1723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["<i>TMEM182<\/i> interacts with integrin beta 1 and regulates myoblast differentiation and muscle regeneration"],"prefix":"10.1002","volume":"12","author":[{"given":"Wen","family":"Luo","sequence":"first","affiliation":[{"name":"Lingnan Guangdong Laboratory of Agriculture South China Agricultural University  Guangzhou China"},{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science South China Agricultural University  Guangzhou China"},{"name":"Guangdong Provincial Key Lab of Agro\u2010Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair South China Agricultural University  Guangzhou China"},{"name":"Department of Orthaepedics and Traumatology The Chinese University of Hong Kong  Hongkong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zetong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science South China Agricultural University  Guangzhou China"},{"name":"Guangdong Provincial Key Lab of Agro\u2010Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science South China Agricultural University  Guangzhou China"},{"name":"Guangdong Provincial Key Lab of Agro\u2010Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genghua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science South China Agricultural University  Guangzhou China"},{"name":"Guangdong Provincial Key Lab of Agro\u2010Animal Genomics and Molecular Breeding, and Key Lab of Chicken 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Agricultural University  Guangzhou China"},{"name":"Guangdong Provincial Key Lab of Agro\u2010Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Lingnan Guangdong Laboratory of Agriculture South China Agricultural University  Guangzhou China"},{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science South China Agricultural University  Guangzhou China"},{"name":"Guangdong Provincial Key Lab of Agro\u2010Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair South China Agricultural University  Guangzhou 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