1. Angiotensin II triggers RIPK3-MLKL-mediated necroptosis by activating the Fas/FasL signaling pathway in renal tubular cells
- Author
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Liangbao Zhong, Guojun Li, Li Xiaoyan, Hongwang Cui, Jie Lv, Yongjun Zhu, and Feng Ye
- Subjects
0301 basic medicine ,Male ,Apoptosis ,Biochemistry ,Fas ligand ,Epithelium ,Mice ,0302 clinical medicine ,Fibrosis ,Animal Cells ,Medicine and Health Sciences ,Small interfering RNAs ,Multidisciplinary ,Cell Death ,Chemistry ,Angiotensin II ,Animal Models ,Nucleic acids ,Kidney Tubules ,Experimental Organism Systems ,Cell Processes ,030220 oncology & carcinogenesis ,Receptor-Interacting Protein Serine-Threonine Kinases ,Necroptosis ,Medicine ,Tumor necrosis factor alpha ,Cellular Types ,Anatomy ,Signal Transduction ,Research Article ,Programmed cell death ,Fas Ligand Protein ,Science ,Mouse Models ,Research and Analysis Methods ,Cell Line ,Necrotic Cell Death ,03 medical and health sciences ,RIPK1 ,Model Organisms ,medicine ,Genetics ,Animals ,Humans ,fas Receptor ,Non-coding RNA ,Biology and Life Sciences ,Epithelial Cells ,Kidneys ,Cell Biology ,Renal System ,medicine.disease ,Gene regulation ,Mice, Inbred C57BL ,030104 developmental biology ,Biological Tissue ,Cell culture ,Cancer research ,Animal Studies ,RNA ,Gene expression ,Protein Kinases ,Developmental Biology - Abstract
Our earlier studies proved that RIPK3-mediated necroptosis might be an important mode of renal tubular cell death in rats with chronic renal injury and the necroptotic cell death can be triggered by tumor necrosis factor-α (TNF-α) in vitro, but the triggering role of angiotensin II (AngII), which exerts notable effects on renal cells for the initiation and progression of renal tubulointerstitial fibrosis, is largely unknown. Here, we identified the presence of necroptotic cell death in the tubular cells of AngII-induced chronic renal injury and fibrosis mice and assessed the percentage of necroptotic renal tubular cell death with the disruption of this necroptosis by the addition of necrostatin-1 (Nec-1). Furthermore, the observation was further confirmed in HK-2 cells treated with AngII and RIPK1/3 or MLKL inhibitors. The detection of Fas and FasL proteins led us to investigate the contribution of the Fas/FasL signaling pathway to AngII-induced necroptosis. Disruption of FasL decreased the percentage of necroptotic cells, suggesting that Fas and FasL are likely key signal molecules in the necroptosis of HK-2 cells induced by AngII. Our data suggest that AngII exposure might trigger RIPK3-MLKL-mediated necroptosis in renal tubular epithelial cells by activating the Fas/FasL signaling pathway in vivo and in vitro.
- Published
- 2019