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Title: Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206(+) M2-like macrophage polarization
Authors: Wang, J
Xu, LZ
Xiang, Z 
Ren, Y
Zheng, XF
Zhao, QY
Zhou, QZ
Zhou, YF
Xu, L
Wang, YP
Issue Date: 2020
Source: Cell death & disease, 19 Feb. 2020, v. 11, 136, p. 1-15
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-beta 1/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.
Publisher: Nature Publishing Group
Journal: Cell death & disease 
ISSN: 2041-4889
DOI: 10.1038/s41419-020-2329-z
Rights: © The Author(s) 2020
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
The following publication Wang, J., Xu, L., Xiang, Z. et al. Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206+ M2-like macrophage polarization. Cell Death Dis 11, 136 (2020) is available at
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