Quandong Hu1, Zhenzhen Hu1, Qiongfeng Chen1, Yonghong Huang2, Zi Mao3, Fangyun Xu1, Xiaoyan Zhou4. 1. Department of Pathophysiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, PR China. 2. Department of Pathophysiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, PR China; Jiangxi Province Key Laboratory of Tumor pathogenesis and Molecular Pathology, Nanchang, Jiangxi 330006, PR China. 3. The First Clinical Medical College, Nanchang University, Jiangxi 330006, PR China. 4. Department of Pathophysiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, PR China; Jiangxi Province Key Laboratory of Tumor pathogenesis and Molecular Pathology, Nanchang, Jiangxi 330006, PR China. Electronic address: zhouxiaoyan@ncu.edu.cn.
Abstract
BACKGROUND: It was recently reported Lipoxins (LXs) had protective effects on fibrous diseases, and renin-angiotensin-aldosterone system (RAAS) had played vital and bidirectional roles in hepatic fibrosis. In this paper, a hepatic fibrosis model, induced by carbon tetrachloride (CCL4) in rats, was used to observe the relations between RAAS and LXs, as well as to further explore the alternative anti-fibrosis mechanisms of LXs. METHODS: The model was evaluated by morphological observations and biochemical assays. The activities and contents of angiotensin converting enzyme (ACE) and angiotensin converting enzyme 2 (ACE2) were examined through assay kits and ELISA. The expression levels of angiotensinII (AngII), Angiotensin II type 1 receptor (AT1R), angiotensin-(1-7) (Ang-1-7), and Mas were all measured using real time PCR, ELISA, and Western blot. RESULTS: The model was established successfully and BML-111 significantly ameliorated CCL4-induced hepatic fibrosis, including reduction inflammation injury, decrease extracellular matrix deposition, and improvement hepatic functions. Furthermore, BML-111 could obviously decrease not only the activities of ACE but also the expression levels of ACE, AngII,and AT1R, which were induced by CCL4. On the other hand, BML-111 could markedly increase the activities of ACE2, besides the expression levels of ACE2, Ang-(1-7) and Mas. More importantly, BOC-2, a lipoxin A4 receptor blocker, could reverse all these phenomena. CONCLUSIONS: Equilibrating ACE-AngII-AT1R axis and ACE2-Ang-(1-7)-Mas axis mediated the protective effect of BML-111 on hepatic fibrosis in rats.
BACKGROUND: It was recently reported Lipoxins (LXs) had protective effects on fibrous diseases, and renin-angiotensin-aldosterone system (RAAS) had played vital and bidirectional roles in hepatic fibrosis. In this paper, a hepatic fibrosis model, induced by carbon tetrachloride (CCL4) in rats, was used to observe the relations between RAAS and LXs, as well as to further explore the alternative anti-fibrosis mechanisms of LXs. METHODS: The model was evaluated by morphological observations and biochemical assays. The activities and contents of angiotensin converting enzyme (ACE) and angiotensin converting enzyme 2 (ACE2) were examined through assay kits and ELISA. The expression levels of angiotensinII (AngII), Angiotensin II type 1 receptor (AT1R), angiotensin-(1-7) (Ang-1-7), and Mas were all measured using real time PCR, ELISA, and Western blot. RESULTS: The model was established successfully and BML-111 significantly ameliorated CCL4-induced hepatic fibrosis, including reduction inflammation injury, decrease extracellular matrix deposition, and improvement hepatic functions. Furthermore, BML-111 could obviously decrease not only the activities of ACE but also the expression levels of ACE, AngII,and AT1R, which were induced by CCL4. On the other hand, BML-111 could markedly increase the activities of ACE2, besides the expression levels of ACE2, Ang-(1-7) and Mas. More importantly, BOC-2, a lipoxin A4 receptor blocker, could reverse all these phenomena. CONCLUSIONS: Equilibrating ACE-AngII-AT1R axis and ACE2-Ang-(1-7)-Mas axis mediated the protective effect of BML-111 on hepatic fibrosis in rats.
Authors: Rafael I Jaén; Sergio Sánchez-García; María Fernández-Velasco; Lisardo Boscá; Patricia Prieto Journal: Front Immunol Date: 2021-04-23 Impact factor: 7.561