In:
Journal of Cellular Biochemistry, Wiley, Vol. 117, No. 1 ( 2016-01), p. 163-171
Abstract:
In recent studies, we found that Numb is involved in oxidative stress‐induced apoptosis of renal proximal tubular cells; however, its function on ER stress‐induced apoptosis in proteinuric kidney disease remains unknown. The objective of the present study is to explore the role of Numb in urinary albumin‐induced apoptosis of human renal tubular epithelial cells (HKCs). In this study, we demonstrate that incubation of HKCs with bovine serum albumin (BSA) resulted in caspase three‐dependent cell death. Numb expression was down‐regulated by BSA in a time‐ and dose‐dependent manner. Knockdown of Numb by siRNA sensitized HKCs to BSA‐induced apoptosis, whereas overexpression of Numb protected HKCs from BSA‐induced apoptosis. Moreover, BSA activated CHOP/PERK signaling pathway in a time‐ and dose‐dependent manner as indicated by increased expression of CHOP, PERK, and P‐PERK. Furthermore, knockdown of CHOP or PERK significantly attenuated the promoting effect of Numb on BSA‐induced apoptosis, while overexpression of CHOP impaired the protective effect of Numb on BSA‐induced apoptosis. Taken together, our findings demonstrate that Numb plays a protective role on BSA‐induced apoptosis through inhibiting CHOP/PERK signaling pathway in human renal tubular epithelial cells. Therefore, the results from this study provides evidence that Numb is a new target of ER‐associated apoptotic signaling networks and Numb may serve as a promising therapeutic target for proteinuric diseases. J. Cell. Biochem. 117: 163–171, 2016. © 2015 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0730-2312
,
1097-4644
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
1479976-5
SSG:
12
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