Qiong-Feng Chen1, Hua Hao2, Xiao-Dong Kuang3, Quan-Dong Hu1, Yong-Hong Huang4, Xiao-Yan Zhou5. 1. Department of Pathophysiology, Medical College of Nanchang University, Nanchang 330006, China. 2. Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China. 3. Department of Pathology, Medical College of Nanchang University, Nanchang 330006, China. 4. Department of Pathophysiology, Medical College of Nanchang University, Nanchang 330006, China; Jiangxi Province Key Laboratory of Tumor Etiology and Molecular Pathology, Nanchang 330006, China. 5. Department of Pathophysiology, Medical College of Nanchang University, Nanchang 330006, China; Jiangxi Province Key Laboratory of Tumor Etiology and Molecular Pathology, Nanchang 330006, China. Electronic address: zhouxiaoyan@ncu.edu.cn.
Abstract
BACKGROUND: The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still. METHODS: We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1-7) (Ang-1-7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot. RESULTS: Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1-7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects. CONCLUSION: BML-111 could protect against acute injury via regulation RAAS.
BACKGROUND: The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still. METHODS: We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1-7) (Ang-1-7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot. RESULTS: Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1-7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects. CONCLUSION: BML-111 could protect against acute injury via regulation RAAS.
Authors: Filipe F Stoyell-Conti; Sarin Itty; Christy Abraham; Katya Rigatto; Crystal A West; Robert C Speth Journal: Endocrine Date: 2021-01-07 Impact factor: 3.633