title: Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.
abstract: Differentiation of muscle satellite cells (MSCs) involves interaction of the proteins present in the extracellular matrix (ECM) with MSCs to regulate their activity, and therefore phenotype. Herein, we report fibromodulin (FMOD), a member of the proteoglycan family participating in the assembly of ECM, as a novel regulator of myostatin (MSTN) during myoblast differentiation. In addition to having a pronounced effect on the expression of myogenic marker genes [myogenin (MYOG) and myosin light chain 2 (MYL2)], FMOD was found to maintain the transcriptional activity of MSTN Moreover, coimmunoprecipitation and in silico studies performed to investigate the interaction of FMOD helped confirm that it antagonizes MSTN function by distorting its folding and preventing its binding to activin receptor type IIB. Furthermore, in vivo studies revealed that FMOD plays an active role in healing by increasing satellite cell recruitment to sites of injury. Together, these findings disclose a hitherto unrecognized regulatory role for FMOD in MSCs and highlight new mechanisms whereby FMOD circumvents the inhibitory effects of MSTN and triggers myoblast differentiation. These findings offer a basis for the design of novel MSTN inhibitors that promote muscle regeneration after injury or for the development of pharmaceutical agents for the treatment of different muscle atrophies.-Lee, E. J., Jan, A. T., Baig, M. H., Ashraf, J. M., Nahm, S.-S., Kim, Y.-W., Park, S.-Y., Choi, I. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, South Korea;
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, South Korea;
authors.forename: Arif Tasleem
authors.initials: AT
authors.lastname: Jan
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, South Korea;
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Baig
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, South Korea;
authors.forename: Jalaluddin Mohammad
authors.initials: JM
authors.lastname: Ashraf
authors.affiliation: College of Veterinary Medicine, Konkuk University, Seoul, South Korea; and.
authors.forename: Sang-Soep
authors.initials: SS
authors.lastname: Nahm
authors.affiliation: Department of Physiology, College of Medicine, Yeungnam University, South Korea.
authors.forename: Yong-Woon
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Yeungnam University, South Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, South Korea; inhochoi@ynu.ac.kr.
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D002460:Cell Line; D003094:Collagen; D000071235:Fibromodulin / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D005819:Genetic Markers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000502:physiology; D009133:Muscular Atrophy / Q000378:metabolism; D032446:Myoblasts / Q000502:physiology; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*
chemical_list: C000604332:Fmod protein, mouse; D005819:Genetic Markers; D055435:Myostatin; D000071235:Fibromodulin; D003094:Collagen
keywords: ACRVIIB; extracellular matrix; myogenesis; myostatin