title: Myostatin and its precursor protein are increased in the skeletal muscle of patients with Type-II muscle fibre atrophy.
abstract: Preferential atrophy of Type-II muscle fibres occurs in several clinical situations, including cachexia, muscle disuse, chronic glucocorticoid treatment, remote neoplasia, and sometimes as an aspect of recent-denervation. For the patient, the Type-II atrophy itself might be unfavourable (as a glucocorticoid side-effect) or favourable (survivalistic via the muscle-alanine liver-gluconeogenesis pathway in starvation). The cellular mechanisms underlying Type-II fibre atrophy are unclear. Myostatin (Mstn) is physiologically a negative regulator of muscle mass and strength. In this study we evaluated a possible role of Mstn in Type-II fibre atrophy in human muscle. Mstn and Mstn precursor protein (MstnPP) were studied in 10-muscle biopsies containing Type-II fibre atrophy and in 17 disease and normal control muscle biopsies. When comparison was made with normal control fibres, we found the following: 1) by immunocytochemistry, diffusely increased Mstn/MstnPP in the atrophic Type-II muscle fibres; 2) by immunoblots, Mstn/MstnPP increased individually; 3) by RT-PCR, no increase in MstnPP mRNA. In conclusion, our results a) suggest that Mstn/ /MstnPP might play a role in the pathogenic cascade of Type-II muscle fibre atrophy; b) broaden our previously-described associations of Mstn in human muscle pathology, and c) could possibly lead to clinical prevention when Type-II muscle fibre atrophy is unfavourable, for instance in glucocorticoid therapy.
authors.affiliation: USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA 90017-1912, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wójcik
authors.forename: A
authors.initials: A
authors.lastname: Nogalska
authors.forename: W K
authors.initials: WK
authors.lastname: Engel
authors.forename: V
authors.initials: V
authors.lastname: Askanas
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001706:Biopsy; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D055435:Myostatin; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; C525911:MSTN protein, human; D055435:Myostatin; D011498:Protein Precursors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000251:Adenosine Triphosphatases