2. Academic Validation
  3. BML-111, a lipoxin receptor agonist, protects against acute injury via regulating the renin angiotensin-aldosterone system

BML-111, a lipoxin receptor agonist, protects against acute injury via regulating the renin angiotensin-aldosterone system

  • Prostaglandins Other Lipid Mediat. 2019 Feb;140:9-17. doi: 10.1016/j.prostaglandins.2018.11.001.
Qiong-Feng Chen 1,  Hua Hao 2,  Xiao-Dong Kuang 3,  Quan-Dong Hu 1,  Yong-Hong Huang 4,  Xiao-Yan Zhou 5
Affiliations

Affiliations

  • 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: [email protected].
PMID: 30412790 DOI: 10.1016/j.prostaglandins.2018.11.001
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.

Keywords

Inflammation; Lipoxins; Renin angiotensin-aldosterone system.

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