Important role of apoptosis signal-regulating kinase 1 in ischemic acute kidney injury |
| |
| Authors: | Terada Yoshio Inoshita Seiji Kuwana Hitoshi Kobayashi Takahiko Okado Tomokazu Ichijo Hidenori Sasaki Sei |
| |
| Institution: | a Department of Nephrology and Blood Purification, Tokyo Medical and Dental University, 5-45, Yushima 1-chome, Bunkyo-ku, Tokyo 113-8519, Japan
b Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan |
| |
| Abstract: | We investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Blood urea nitrogen (BUN) and serum creatinine were significantly higher in ASK1+/+ mice than in ASK1−/− mice after I/R injury. Renal histology of ASK1+/+ mice showed significantly greater tubular necrosis and degradation. In ASK1−/− mice, phosphorylation of ASK1, JNK, and p38K, and the number of TUNEL-positive cells and infiltrated leukocytes decreased after I/R injury. Apoptotic changes were significantly decreased in cultured renal tubular epithelial cells (TECs) from ASK1−/− mice under hypoxic condition. Transfection with dominant-active ASK1 induced apoptosis in TECs. Protein expression of monocyte chemoattractant protein-1 (MCP-1) was significantly weaker in ASK1−/− mice after I/R injury. Transfection with dominant negative-ASK1 significantly decreased MCP-1 production in TECs. These results demonstrated that ASK1 is activated in I/R-induced AKI, and blockage of ASK1 attenuates renal tubular apoptosis, MCP-1 expression, and renal function. |
| |
| Keywords: | AKI Apoptosis Renal tubules Caspase |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
