期刊
KIDNEY INTERNATIONAL
卷 93, 期 1, 页码 173-187出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2017.07.026
关键词
macrophage-myofibroblast transition (MMT); single-cell RNA sequencing; Src
资金
- Research Grants Council of Hong Kong [CUHK3/CRF/12R, GRF 468513, 14117815, T12-402/13N]
- Focused Investment Scheme A and VC's One-off Discretionary Fund from Chinese University of Hong Kong [VCF2014008-CUHK]
Src activation has been associated with fibrogenesis after kidney injury. Macrophage-myofibroblast transition is a newly identified process to generate collagen-producing myofibroblasts locally in the kidney undergoing fibrosis in a TGF-beta/Smad3-dependent manner. The potential role of the macrophage-myofibroblast transition in Src-mediated renal fibrosis is unknown. In studying this by RNA sequencing at single-cell resolution, we uncovered a unique Src-centric regulatory gene network as a key underlying mechanism of macrophage-myofibroblast transition. A total of 501 differentially expressed genes associated with macrophage-myofibroblast transition were identified. However, Smad3-knockout largely reduced the transcriptome diversity. More importantly, inhibition of Src largely suppresses ureteral obstruction-induced macrophage-myofibroblast transition in the injured kidney in vivo along with transforming growth factor-beta 1-induced elongated fibroblast-like morphology, alpha-smooth muscle actin expression and collagen production in bone marrow derived macrophages in vitro. Unexpectedly, we further uncovered that Src serves as a direct Smad3 target gene and also specifically up-regulated in macrophages during macrophage-myofibroblast transition. Thus, macrophage-myofibroblast transition contributes to Src-mediated tissue fibrosis. Hence, targeting Src may represent as a precision therapeutic strategy for macrophage-myofibroblast transition-driven fibrotic diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据