title: Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl₄-Induced Skeletal Muscle Injury.
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.
authors: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. c3602@naver.com.
authors: Ok-Kyung
authors: OK
authors: Hwang
authors: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. jinkyu820@knu.ac.kr.
authors: Jin-Kyu
authors: JK
authors: Park
authors: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. nikeun@hanmail.net.|Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Korea. nikeun@hanmail.net.
authors: Eun-Joo
authors: EJ
authors: Lee
authors: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. nikeun@hanmail.net.|Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Korea. nikeun@hanmail.net.
authors: Eun-Mi
authors: EM
authors: Lee
authors: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. pretersensual@hanmail.net.|Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Korea. pretersensual@hanmail.net.
authors: Ah-Young
authors: AY
authors: Kim
authors: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. jeongks@knu.ac.kr.|Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Korea. jeongks@knu.ac.kr.
authors: Kyu-Shik
authors: KS
authors: Jeong
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology*; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism; D010766:Phosphorylation; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D016189:Dystrophin; D017570:MyoD Protein; D018008:Myogenin; D051763:PAX7 Transcription Factor; D051899:Smad2 Protein; D051900:Smad3 Protein; D002251:Carbon Tetrachloride; D019808:Losartan
keywords: CCl4; TGF-β1; losartan; skeletal muscle