Role of AT1 receptor autoantibody in irbesartan-inhibited signaling of endoplasmic reticulum stress in rat kidney with diabetic nephropathy
10.3760/cma.j.issn.1000-6699.2015.05.005
- VernacularTitle:AT1受体自身抗体对厄贝沙坦抑制糖尿病肾病大鼠肾脏内质网应激相关信号的影响
- Author:
Chunyan XU
;
Linshuang ZHAO
;
Dezhong LI
- Publication Type:Journal Article
- Keywords:
AT1 receptor autoantibody;
Irbesartan;
Endoplasmic reticulum stress;
Apoptosis;
Diabetic nephropathy
- From:
Chinese Journal of Endocrinology and Metabolism
2015;31(5):400-405
- CountryChina
- Language:Chinese
-
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.
