The nephroprotective effect of tauroursodeoxycholic acid on ischaemia/reperfusion-induced acute kidney injury by inhibiting endoplasmic reticulum stress.
The incidence of acute kidney injury (AKI) is very high, and multiple physiopathological processes are involved, including endoplasmic reticulum stress (ERS). Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid derivative that has been reported to inhibit ERS. To determine whether TUDCA had a nephroprotective effect on AKI and to explore the exact mechanism, an ischaemia/reperfusion (I/R)-induced AKI mouse model and a tunicamycin-pre-treated TCMK-1 cell model were established. It was found that the renal tubular necrosis score and cell apoptosis index reached their peak 24 hr after I/R. GRP78 and C/EBP homologous protein (CHOP) expression and Caspase 12 activation were enhanced, reaching their peaks at 4 and 12 hr, respectively. TUDCA intervention not only decreased the renal tubular necrosis score and the cell apoptosis index but also down-regulated GRP78 and CHOP expression and Caspase 12 activation. The survival rate of TCMK-1 cells pre-treated with TUDCA was significantly higher than that of TCMK-1 cells without TUDCA pre-treatment. In conclusion, TUDCA had a nephroprotective effect on IR-induced AKI by inhibiting ERS and by blocking GRP78 and CHOP expression, reducing Caspase 12 activation and inhibiting cell apoptosis.
Kidney institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, China.
Xiang
X
Gao
Lili
L
Fu
Min
M
Xiao
Chenggang
C
Xu
Lijun
L
Sun
Tong
T
Zhang
Feng
F
Zheng
Changlin
C
Mei
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000188:drug therapy*; D013312:Stress, Physiological / Q000187:drug effects*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D051742:Transcription Factor CHOP; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C506440:Casp12 protein, mouse; D053454:Caspase 12