Journal of Applied Physiology
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J Appl Physiol 104: 170-177, 2008. First published October 4, 2007; doi:10.1152/japplphysiol.00463.2006
8750-7587/08 $8.00
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TGF-β1 and TNF-{alpha} are involved in the transcription of type I collagen {alpha}2 gene in soleus muscle atrophied by mechanical unloading

Tatsuro Hirose,1 Koichi Nakazato,2 Hongsun Song,2 and Naokata Ishii1

1Department of Life Science, Graduate School of Arts and Science, The University of Tokyo; and 2Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan

Submitted 23 April 2006 ; accepted in final form 28 September 2007

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)-β1, -β2, and -β3, 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-β1, TGF-β3, and Smad3, positive regulatory factors for COL1A2, increased at day 7. The in situ hybridization for COL1A2 and the immunohistochemistry of TGF-β1 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-β/Smad pathway.

muscle atrophy; microgravity; extracellular matrix


Address for reprint requests and other correspondence: T. Hirose, Dept. of Life Science, Graduate School of Arts and Science, The Univ. of Tokyo, 3-8-1 Komaba, Meguro-ku, 153-8902 Tokyo, Japan (e-mail: thirose{at}nittai.ac.jp)






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