Role of AT1 receptor autoantibody in irbesartan-inhibited signaling of endoplasmic reticulum stress in rat kidney with diabetic nephropathy / 中华内分泌代谢杂志
Chinese Journal of Endocrinology and Metabolism
; (12): 400-405, 2015.
Article
in Zh
| WPRIM
| ID: wpr-468520
Responsible library:
WPRO
ABSTRACT
Objective To investigate the role of AT1 receptor autoantibody (AT1-AA) in the inhibitory action of irbesartan on endoplasmic reticulum stress (ERS)-related apoptotic signals in rat kidney with diabetic nephropathy (DN).Methods DN model rats were induced by high-sugar and high-fat diet plus intraperitoneal injection of streptozotocin,and the serum level of AT1-AA was detected by ELISA.These DN rats with positive or negative AT1-AA were divided into DN group and irbesartan treated group.After 4 weeks of irbesartan treatment,TUNEL staining was used to detect renal cell apoptosis.The protein and mRNA expressions of ERS chaperone protein glucose-regulated protein 78 (GRP78) and ERS-associated apoptosis proteins were determined by Western blot and RT-PCR.Results Compared with NC group,the apoptosis rate of renal cells in DN group was obviously increased,along with the increased expressions of GRP78,C/EBP homology protein (CHOP),phosphorylated c-Jun N-terminal kinase (JNK),and Caspase12 protein and mRNA (all P<0.01).The cell apoptosis and protein and mRNA levels of these genes were significantly decreased after irbesartan treatment (all P< 0.01),especially in AT1-AA positive DN rats(all P<0.05).The renal cell apoptosis rate,and protein and mRNA levels of these four genes in AT1-AA positive DN group were much greater than those in AT1-AA negative DN group (all P<0.05).Conclusions AT1-AA may be involved in ERS-related cell apoptosis in the kidney of DN rats,and play a role in irbesartan-improved renal function via inhibiting ERS-associated CHOP-JNK-Caspase12 apoptotic signals and renal cell apoptosis.
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WPRIM
Language:
Zh
Journal:
Chinese Journal of Endocrinology and Metabolism
Year:
2015
Type:
Article