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The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring.

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资源类型：
Pubmed体系：
作者：
Patrick Ming-Kuen Tang[1,2] ; Shuang Zhou[2,3] ; Chun-Jie Li[2,4] ; Jinyue Liao[6] ; Jun Xiao[2] ; Qing-Ming Wang[2] ; Guang-Yu Lian[2] ; Jinhong Li[2] ; Xiao-Ru Huang[2] ; Ka-Fai To[1] ; Chi-Fai NG[5] ; Charing Ching-Ning Chong[5] ; Ronald Ching-Wa Ma[2] ; Tin-Lap Lee[6] ; Hui-Yao Lan[2,*1] ;
机构： [1]Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China [2]Li Ka Shing Institute of Health Sciences, and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China [3]Clinical Translational Research Center, Shanghai Pulmonary Hospital, and Department of Histology and Embryology, Tongji University School of Medicine, Tongji University Cancer Institute, Shanghai, China [4]Department of Head and Neck Oncology, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China [5]Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China [6]Reproduction, Development and Endocrinology Program, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
出处：
DOI： 10.1016/j.kint.2017.07.026
ISSN：

关键词： macrophage-myofibroblast transition (MMT) single-cell RNA sequencing Src

摘要：
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-β/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-β1-induced elongated fibroblast-like morphology, α-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. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

基金：
This study is supported by the Research Grants Council of Hong Kong (CUHK3/ CRF/12R, GRF 468513, 14117815, T12–402/13N), and the Focused Investment Scheme A and VC’s One-off Discretionary Fund (VCF2014008-CUHK) from Chinese University of Hong Kong.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类 | 1 区 医学
小类 | 1 区 泌尿学与肾脏学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 泌尿学与肾脏学
第一作者：
第一作者机构： [1]Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China [2]Li Ka Shing Institute of Health Sciences, and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
共同第一作者：
通讯作者：
通讯机构： [2]Li Ka Shing Institute of Health Sciences, and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China [*1]Li Ka Shing Institute of Health Sciences, and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
推荐引用方式(GB/T 7714)：
Patrick Ming-Kuen Tang,Shuang Zhou,Chun-Jie Li,et al.The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring.[J].Kidney international.2018,93(1):173-187.doi:10.1016/j.kint.2017.07.026.
APA：
Patrick Ming-Kuen Tang,Shuang Zhou,Chun-Jie Li,Jinyue Liao,Jun Xiao...&Hui-Yao Lan.(2018).The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring..Kidney international,93,(1)
MLA：
Patrick Ming-Kuen Tang,et al."The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring.".Kidney international 93..1(2018):173-187

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