title: TGF-beta1 and TNF-alpha are involved in the transcription of type I collagen alpha2 gene in soleus muscle atrophied by mechanical unloading.
abstract: The aim of this study was to examine the effect of hindlimb suspension (HS) on the expressions of COL1A2 (type I collagen alpha(2) chain) mRNA and its regulatory factors, transforming growth factors (TGF)-beta(1), -beta(2), and -beta(3), phosphorylated Smad3, and tumor necrosis factor-alpha (TNF-alpha) in rat hindlimb muscles. Forty-eight male Wistar rats (age, 5 wk) were randomly assigned to HS for 1, 3, 7, and 14 days and control (n = 6 for each). During the exposure to HS, COL1A2 mRNA expression decreased in the soleus muscle at day 3 and recovered to control level at day 7. The content of TNF-alpha, one of the negative regulatory factors for COL1A2, increased from day 3 until day 14. On the other hand, the contents of TGF-beta(1), TGF-beta(3), and Smad3, positive regulatory factors for COL1A2, increased at day 7. The in situ hybridization for COL1A2 and the immunohistochemistry of TGF-beta(1) and TNF-alpha revealed their expressions around nerve-related tissues, including muscle spindles and connective tissue sheath. The results indicate that the transcriptional activity of COL1A2 in the soleus muscle initially decreases in response to unloading through an increase in TNF-alpha production; thereafter, it returns toward normal level through the activated TGF-beta/Smad pathway.
authors.affiliation: Dept. of Life Science, Graduate School of Arts and Science, The Univ. of Tokyo, 3-8-1 Komaba, Meguro-ku, 153-8902 Tokyo, Japan. thirose@nittai.ac.jp
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Hirose
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakazato
authors.forename: Hongsun
authors.initials: H
authors.lastname: Song
authors.forename: Naokata
authors.initials: N
authors.lastname: Ishii
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D019417:Hindlimb Suspension; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat