Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway  

作　　者：Yu-han Zhang Ya-qin Zhang Cong-cong Guo Li-kang Wang Yu-jiao Cui Jian-jun Dong Lin Liao 

机构地区：[1]Division of Endocrinology,Department of Internal Medicine,Shandong Provincial Qianfoshan Hospital,Shandong University,Ji-nan 250014,China [2]Division of Endocrinology,Department of Internal Medicine,Wuhan Third Hospital,Wuhan 430060,China [3]First Clinical Medical College,Shandong University of Traditional Chinese Medicine,Ji-nan 250355,China [4]Department of Endocrinology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Ji-nan 250011,China [5]Division of Endocrinology,Department of Internal Medicine,Qilu Hospital of Shandong University,Ji-nan 250012,China [6]Division of Endocrinology,Department of Internal Medicine,the First Af?liated Hospital of Shandong First Medical University,Ji-nan 250014,China

出　　处：《Acta Pharmacologica Sinica》2020年第4期561-571,共11页中国药理学报（英文版）

基　　金：funded by National Natural Science Foundation of China(81670757,81570742);the Shandong Provincial Natural Science Foundation(ZR2016HQ26);the Grant for the Development of Science and Technology of Ji-nan City(201602172).

摘　　要：Proximal renal tubular damage is a critical process underlying diabetic kidney disease(DKD).Our previous study shows that prostaglandin E1(PGE1)reduces the apoptosis of renal tubular cells in DKD rats.But its underlying mechanisms remain unclear.In this study we investigated the protective effects of PGE1 in DKD rats and high glucose(HG,30 mM)-treated HK-2 proximal tubular cells.Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established,the DKD rats were administered PGE1(10μg·kg^?1·d^?1,iv.)for 10 consecutive days.We showed that PGE1 administration did not change blood glucose levels,but alleviated diabetic kidney injury in the DKD rats,evidenced by markedly reduced proteinuria and renal tubular apoptosis.In the in vitro experiments,PGE1(0.1–100μM)signi?cantly enhanced HG-reduced HK-2 cell viability.In HG-treated HK-2 cells,PGE1(10μM)signi?cantly suppressed the c-Jun N-terminal kinase(JNK)and the mitochondrial apoptosis-related protein expressions such as Bim,Bax,caspase-3 and cleaved caspase-3;similar changes were also observed in the kidney of PGE1-treated DKD rats.By using two pharmacological tools-JNK activator anisomycin(AM)and JNK inhibitor SP600125,we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells;JNK was an upstream regulator of Bim.In conclusion,our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling.

关 键 词：Diabetic kidney disease PROXIMAL renal TUBULAR CELLS prostaglandin E1 apoptosis JNK/Bim HK-2 PROXIMAL TUBULAR CELLS ANISOMYCIN SP600125 

分 类 号：R363[医药卫生—病理学]