title: Numb Protects Human Renal Tubular Epithelial Cells From Bovine Serum Albumin-Induced Apoptosis Through Antagonizing CHOP/PERK Pathway.
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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou, Zhengzhou, 450052, Henan, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou, Zhengzhou, 450052, Henan, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Shao
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, 58108, North Dakota.
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou, Zhengzhou, 450052, Henan, China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D051742:Transcription Factor CHOP; D012710:Serum Albumin, Bovine; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase; D053148:Caspase 3
keywords: APOPTOSIS; BSA; CHOP/PERK PATHWAY; NUMB