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Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and kidney fibrosis
Author(s) -
Ren Jiafa,
Li Jianzhong,
Feng Ye,
Shu Bingyan,
Gui Yuan,
Wei Wei,
He Weichun,
Yang Junwei,
Dai Chunsun
Publication year - 2017
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4921
Subject(s) - mtorc2 , pi3k/akt/mtor pathway , cancer research , fibrosis , macrophage polarization , macrophage , growth factor , biology , microbiology and biotechnology , immunology , medicine , signal transduction , mtorc1 , receptor , biochemistry , in vitro
Mammalian target of rapamycin (mTOR) signalling controls many essential cellular functions. However, the role of Rictor/mTOR complex 2 (mTORC2) in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction or ischaemia/reperfusion injury. In bone marrow‐derived macrophages (BMMs), deletion of Rictor or blockade of protein kinase Cα inhibited cell migration. Additionally, deletion of Rictor or blockade of Akt abolished interleukin‐4‐stimulated or transforming growth factor (TGF)‐β1‐stimulated macrophage M2 polarization. Furthermore, deletion of Rictor downregulated TGF‐β1‐stimulated upregulation of multiple profibrotic cytokines, including platelet‐derived growth factor, vascular endothelial growth factor and connective tissue growth factor, in BMMs. Conditioned medium from TGF‐β1‐pretreated Rictor –/– macrophages stimulated fibroblast activation less efficiently than that from TGF‐β1‐pretreated Rictor +/+ macrophages. These results demonstrate that Rictor/mTORC2 signalling can promote macrophage activation and kidney fibrosis. Targeting this signalling pathway in macrophages may shine light on ways to protect against kidney fibrosis in patients with chronic kidney diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.