Int J Sports Med 2011; 32(10): 735-742
DOI: 10.1055/s-0031-1279771
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Antifibrotic Effects of Smad4 Small Interfering RNAs in Injured Skeletal Muscle After Acute Contusion

H. Li1 , J. Chen1 , S. Chen1 , Q. Zhang1 , S. Chen1
  • 1Sports Medicine Center of Fudan University, Department of Sports Medicine, Huashan Hospital, Shanghai, China
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Publication History

accepted after revision May 02, 2011

Publication Date:
12 September 2011 (online)

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Abstract

Muscle injuries are common musculoskeletal problems encountered in sports medicine clinics. In this study, we examined the effect of lentivirus-mediated small interfering RNA (siRNA) targeting Smad4 on the suppression of the fibrosis in injured skeletal muscles. We found that Smad4-siRNA could efficiently knock down the expression of Smad4 in the C2C12 myoblast cells and in the contunded mice gastrocnemius muscle. The expression of mRNA level of Smad4 decreased to 11% and 49% compared to the control group, respectively, and the expression of protein level decreased to 13% and 57% respectively. Moreover, the lentivirus-mediated siRNA was stably transfected only into the skeletal muscle and not into the liver of the animals. In contunded mice gastrocnemius, the collagenous and vimentin-positive area in the Smad4 siRNA group reduced to 36% and 37% compared to the control group, respectively. Furthermore, compared to the scrambled Smad4 siRNA-injected mice and PBS control-injected mice, the muscle function of the mice injected with lentivirus-mediated Smad4 siRNA improved in terms of both fast-twitch and tetanic strength (P<0.05). The results suggest that the gene therapy of inhibiting Smad4 by lentivirus-mediated siRNA could be a useful approach to prevent scar tissue formation and improve the function of injured skeletal muscle.

References

Correspondence

Dr. Jiwu Chen

Sports Medicine Center of

Fudan University

Department of Sports Medicine

Huashan Hospital

No. 12 Urumq Middle Road

Shanghai

China

200040 Shanghai

China

Phone: + 86/21/5288 7113

Fax: + 86/21/6249 6020

Email: jeevechan@yahoo.com.cn