期刊
LIFE SCIENCES
卷 258, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118175
关键词
Podocytes; Angiotensin II; Cell survival; Renal disease; Tmem63c
资金
- DFG (German Research Foundation) [394046635 - SFB 1365]
Aims: Human podocytes (hPC) play an important role in the pathogenesis of renal diseases. In this context, angiotensin II (Ang II) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF kappa B) play a crucial role in podocyte injury. Recently, transmembrane protein (Tmem) 63c, a member of the Tmem-family was found to be expressed in kidney and associated with podocyte function. In this study, we analysed the expression regulation and functional impact of Tmem63c on cell viability and apoptosis in hPC in the context of Ang II activation. Materials and methods: Expression of Tmem63c in response to Ang II and the NF kappa B inhibitor Bay 11-7082 was analysed by Real-Time PCR and Western blotting. Cellular functions were determined by functional assays. Key findings: We found Ang II to induce Tmem63c expression in hPC in a concentration-dependent manner. Inhibition of NF kappa B by Bay 11-7082 reduced basal as well as Ang II-induced Tmem63c expression. SiRNA-mediated down-regulation of Tmem63c diminished cell viability and protein kinase B (Akt) signaling and increased cell apoptosis of resting as well as Ang II-activated hPC. Significance: These data show that Ang II induced the expression of Tmem63c in hPC, possibly via NF kappa B-dependent mechanisms. Moreover, down-regulation of Tmem63c was associated with reduced cell viability, indicating Tmem63c to be a potential pro-survival factor in hPC.
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