TGF- beta sub(1) and TNF- alpha are involved in the transcription of type I collagen alpha sub(2) gene in soleus muscle atrophied by mechanical unloading

• Published in: Journal of applied physiology (1985) Vol. 104; no. 1; pp. 170 - 177
• Main Authors: Hirose, Tatsuro, Nakazato, Koichi, Song, Hongsun, Ishii, Naokata
• Format: Journal Article
• Language: English
• Published: 01.01.2008
• ISSN: 8750-7587; 1522-1601

The aim of this study was to examine the effect of hindlimb suspension (HS) on the expressions of COL1A2 (type I collagen alpha sub(2) chain) mRNA and its regulatory factors, transforming growth factors (TGF)- beta sub(1), - beta sub(2), and - beta sub(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 sub(1), TGF- beta sub(3), and Smad3, positive regulatory factors for COL1A2, increased at day 7. The in situ hybridization for COL1A2 and the immunohistochemistry of TGF- beta sub(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.