2. Academic Validation
  3. MCTR3 reduces LPS-induced acute lung injury in mice via the ALX/PINK1 signaling pathway

MCTR3 reduces LPS-induced acute lung injury in mice via the ALX/PINK1 signaling pathway

  • Int Immunopharmacol. 2021 Jan:90:107142. doi: 10.1016/j.intimp.2020.107142.
Rong Zhuang 1,  Xiyu Yang 2,  Wenchao Cai 2,  Rongxiao Xu 2,  Liang Lv 2,  Yingying Sun 2,  Yayong Guo 2,  Jingjing Ni 2,  Guangju Zhao 2,  Zhongqiu Lu 3
Affiliations

Affiliations

  • 1 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Anesthesiology, Critical Care and Pain Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 33268042 DOI: 10.1016/j.intimp.2020.107142
Abstract

Acute lung injury (ALI), a common respiratory distress syndrome in the intensive care unit (ICU), is mainly caused by severe Infection and shock. Epithelial and capillary endothelial cell injury, interstitial edema and inflammatory cell infiltration are the main pathological changes observed in ALI animal models. Maresin conjugates in tissue regeneration (MCTR) are a new family of anti-inflammatory proteins. MCTR3 is a key enhancer of the host response, that promotes tissue regeneration and reduces infection; however, its role and mechanism in ALI are still unclear. The purpose of our research was to assess the protective effects of MCTR3 against ALI and its underlying mechanism. The work in this study was conducted in a murine model and the pulmonary epithelial cell line MLE-12. In vivo, MCTR3 (2 ng/g) was given 2 h after lipopolysaccharide (LPS) injection. We found that the treatment of mice with LPS-induced ALI with MCTR3 significantly reduced the cell number and protein levels in the bronchoalveolar lavage fluid (BALF); decreased the production of inflammatory cytokines; alleviated oxidative stress and cell Apoptosis, consequently decreased lung injury; and restored pulmonary function. These protective effects of MCTR3 were dependent on down-regulation of the PTEN-induced putative kinase 1 (PINK1) pathway. Additionally, in MLE-12 cells stimulated with LPS, MCTR3 inhibited cell death, inflammatory cytokine levels and oxidative stress via the ALX/PINK1 signaling pathway. Thus, we conclude that MCTR3 protected against LPS-induced ALI partly through inactivation of the ALX/PINK1 mediated Mitophagy pathway.

Keywords

Acute lung injury; Inflammation; LPS; MCTR3; PINK1.

Figures
Products