Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206+ M2-like macrophage polarization

Jie Wang, Lizhi Xu, Zou Xiang, Yan Ren, Xiufen Zheng, Qingya Zhao, Qunzhi Zhou, Yuefen Zhou, Lin Xu, Yaping Wang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

6 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix deposition with limited treatment options. Based on our previous observation, we hypothesized microcystin-leucine arginine (LR), an environmental cyanobacterial toxin, could potentially suppress pulmonary fibrosis. In this study, we first demonstrated that chronic exposure of microcystin-LR by oral for weeks indeed attenuated the pulmonary fibrosis both on bleomycin-induced rat and fluorescein isothiocyanate-induced mouse models. Our data further indicated that treatment with microcystin-LR substantially reduced TGF-β1/Smad signaling in rat pulmonary tissues. The experiments in vitro found that microcystin-LR was capable of blocking epithelial–mesenchymal transition (EMT) and fibroblast–myofibroblast transition (FMT) through suppressing the differentiation of CD206+ macrophages. Mechanically, microcystin-LR was found to bind to glucose-regulated protein 78 kDa (GRP78) and suppress endoplasmic reticulum unfolded protein response (UPRER) signaling pathways. These events led to the modulation of M2 polarization of macrophages, which eventually contributed to the alleviation of pulmonary fibrosis. Our results revealed a novel mechanism that may account for therapeutic effect of microcystin-LR on IPF.

Original languageEnglish
Article number136
JournalCell Death and Disease
Volume11
Issue number2
DOIs
Publication statusPublished - 19 Feb 2020

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this