ReferenceID 6055
Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway
Acta Pharmacol Sin
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 underl
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Record Fields
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- Reference Id
- 6055
- Evidence Id
- 22645
- Core Evidence Id
- 22645
- Source Reference Id
- 5372
- Herb2 Reference Id
- HBREF006169
- Subject Paper Key
- HBIN040885_31685975
- Pubmed Id
- 31685975
- Doi
- 10.1038/s41401-019-0314-9
- Paper Title
- Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway
- Paper Abstract
- 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 (10 microg 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 (0.1-100 microM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 microM) significantly 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 pathway.
- Journal
- Acta Pharmacol Sin
- Publish Year
- 2020
- Experiment Subject
- rat; hg-treated hk-2 cells; hk-2 cells; hk-2 proximal tubular cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Proteinuria; Proximal Renal Tubular Damage; Diabetic Kidney Disease; Diabetic Kidney Injury
- Paper Title Cn
- Paper Title En
- Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway
- Bilingual Status
- semi_complete