https://scholars.lib.ntu.edu.tw/handle/123456789/637604
標題: | Role of Calbindin-D28k in Diabetes-Associated Advanced Glycation End-Products-Induced Renal Proximal Tubule Cell Injury | 作者: | KUO-HOW HUANG Guan, Siao-Syun Lin, Wei-Han Wu, Cheng-Tien Sheu, Meei-Ling Chiang, Chih-Kang Liu, Shing-Hwa |
關鍵字: | advanced glycation end products; calbindin-D28k; diabetic nephropathy; renal fibrosis; renal proximal tubule | 公開日期: | 30-六月-2019 | 卷: | 8 | 期: | 7 | 來源出版物: | Cells | 摘要: | Diabetes-associated advanced glycation end-products (AGEs) can increase extracellular matrix (ECM) expression and induce renal fibrosis. Calbindin-D28k, which plays a role in calcium reabsorption in renal distal convoluted tubules, is increased in a diabetic kidney. The role of calbindin-D28k in diabetic nephropathy still remains unclear. Here, calbindin-D28k protein expression was unexpectedly induced in the renal tubules of db/db diabetic mice. AGEs induced the calbindin-D28k expression in human renal proximal tubule cells (HK2), but not in mesangial cells. AGEs induced the expression of fibrotic molecules, ECM proteins, epithelial-mesenchymal transition (EMT) markers, and endoplasmic reticulum (ER) stress-related molecules in HK2 cells, which could be inhibited by a receptor for AGE (RAGE) neutralizing antibody. Calbindin-D28k knockdown by siRNA transfection reduced the cell viability and obviously enhanced the protein expressions of fibrotic factors, EMT markers, and ER stress-related molecules in AGEs-treated HK2 cells. Chemical chaperone 4-Phenylbutyric acid counteracted the AGEs-induced ER stress and ECM and EMT markers expressions. Calbindin-D28k siRNA in vivo delivery could enhance renal fibrosis in db/db diabetic mice. These findings suggest that inducible calbindin-D28k protects against AGEs/RAGE axis-induced ER stress-activated ECM induction and cell injury in renal proximal tubule cells. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637604 | ISSN: | 2073-4409 | DOI: | 10.3390/cells8070660 |
顯示於: | 醫學系 |
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