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Int. J. Mol. Sci. 2016, 17(2), 227; doi:10.3390/ijms17020227

Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl4-Induced Skeletal Muscle Injury

1
Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea
2
Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 31 December 2015 / Revised: 1 February 2016 / Accepted: 3 February 2016 / Published: 8 February 2016
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Abstract

TGF-β1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-β can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl4 intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl4-treatment group (n = 7), and CCl4 + losartan treatment group (n = 7). After CCl4 treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl4 + losartan group (p < 0.01). p(phospho)-Smad2/3 expression significantly increased in the muscles of the control group compared to that in the CCl4 + losartan group (p < 0.01). The expressions of Pax7, MyoD, and myogenin increased in skeletal muscles of the CCl4 + losartan group compared to the corresponding levels in the control group (p < 0.01). We hypothesize that systemically elevated TGF-β1 as a result of CCl4-induced liver injury causes skeletal muscle injury, while losartan promotes muscle repair from injury via blockade of TGF-β1 signaling. View Full-Text
Keywords: CCl4; losartan; skeletal muscle; TGF-β1 CCl4; losartan; skeletal muscle; TGF-β1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hwang, O.-K.; Park, J.-K.; Lee, E.-J.; Lee, E.-M.; Kim, A.-Y.; Jeong, K.-S. Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl4-Induced Skeletal Muscle Injury. Int. J. Mol. Sci. 2016, 17, 227.

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