| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Zhuang, Yibo Jia, Zhanjun Ni, Jiajia Bai, Mi Wang, Rong Zhao, Min Yang, Lingyun Huang, Songming Ding, Guixia Zhang, Aihua |
| Description |
Author Affiliation: Zhuang Y ( From the Department of Nephrology, Nanjing Children's Hospital and the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Ding G ( From the Department of Nephrology, Nanjing Children's Hospital and.); Zhao M ( the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Bai M ( the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Yang L ( the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Ni J ( the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Wang R ( the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Jia Z ( From the Department of Nephrology, Nanjing Children's Hospital and the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Huang S ( From the Department of Nephrology, Nanjing Children's Hospital and the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China.); Zhang A ( From the Department of Nephrology, Nanjing Children's Hospital and the Institute of Pediatrics, Nanjing Medical University, Nanjing 210008, China zhaihua@njmu.edu.cn.) |
| Abstract |
Proteinuria serves as a direct causative factor of renal tubular cell injury and is highly associated with the progression of chronic kidney disease via uncertain mechanisms. Recently, evidence demonstrated that both NLRP3 inflammasome and mitochondria are involved in the chronic kidney disease progression. The present study was undertaken to examine the role of NLRP3 inflammasome/mitochondria axis in albumin-induced renal tubular injury. In patients with proteinuria, NLRP3 was significantly up-regulated in tubular epithelial cells and was positively correlated with the severity of proteinuria. In agreement with these results, albumin remarkably activated NLRP3 inflammasome in both in vitro renal tubular cells and in vivo kidneys in parallel with significant epithelial cell phenotypic alteration and cell apoptosis. Genetic disruption of NLRP3 inflammasome remarkably attenuated albumin-induced cell apoptosis and phenotypic changes under both in vitro and in vivo conditions. In addition, albumin treatment resulted in a significant mitochondrial abnormality as evidenced by the impaired function and morphology, which was markedly reversed by invalidation of NLRP3/caspase-1 signaling pathway. Interestingly, protection of mitochondria function by Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP) or cyclosporin A (CsA) robustly attenuated albumin-induced injury in mouse proximal tubular cells. Collectively, these findings demonstrated a pathogenic role of NLRP3 inflammasome/caspase-1/mitochondria axis in mediating albumin-induced renal tubular injury. The discovery of this novel axis provides some potential targets for the treatment of proteinuria-associated renal injury. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
36 |
| Volume Number |
289 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2014-09-05 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Carrier Proteins Metabolism Inflammasomes Kidney Tubules, Proximal Mitochondria Adolescent Animals Blotting, Western Genetics Caspase 1 Cells, Cultured Child, Preschool Cyclosporine Pharmacology Immunosuppressive Agents Kidney Drug Effects Pathology Membrane Potential, Mitochondrial Physiology Metalloporphyrins Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Proteinuria RNA Interference Serum Albumin, Bovine Toxicity Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
