Therapeutic Effect of Losartan,an Angiotensin II Type 1 Receptor Antagonist,on CCl4-Induced Skeletal Muscle Injury |
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| Authors: | Ok-Kyung Hwang Jin-Kyu Park Eun-Joo Lee Eun-Mi Lee Ah-Young Kim Kyu-Shik Jeong |
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| Affiliation: | 1.Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea; (O.-K.H.); (J.-K.P.); (E.-J.L.); (E.-M.L.); (A.-Y.K.);2.Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Korea |
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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. |
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| Keywords: | CCl4 losartan skeletal muscle TGF-β 1 |
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