| First Author | Liu J | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 5 | Pages | e0197158 |
| PubMed ID | 29746568 | Mgi Jnum | J:265830 |
| Mgi Id | MGI:6158628 | Doi | 10.1371/journal.pone.0197158 |
| Citation | Liu J, et al. (2018) The protective effect of the EP2 receptor on TGF-beta1 induced podocyte injury via the PI3K / Akt signaling pathway. PLoS One 13(5):e0197158 |
| abstractText | Transforming growth factor beta1 (TGF-beta1) plays a central role in chronic kidney diseases. TGF-beta1 induction causes podocyte injury, which results in proteinuria and renal failure. However, the effect of the prostaglandin E2 /E-prostanoid receptor (EP2) on TGF-beta1-induced podocyte injury remains unknown. Previous studies have shown that phosphoinositide 3-OH kinase (PI3K)/Akt is widespread in cells, and is vital for the regulation of cell proliferation, differentiation, apoptosis and metabolism. In this study, we cultured immortalized mouse podocytes in vitro in different groups: control group; TGF-beta1 (5ng/ml) group; EP2 agonist Butaprost treatment (10-7, 10-6, or 10-5mol/L) +TGF-beta1 group; EP2 antagonist AH6809 treatment (10-7, 10-6, or 10-5mol / L) + TGF-beta1 group. We found that compared with the control group, proliferation of podocytes in the TGF-beta1 group significantly decreased and apoptosis increased. Expression of cAMP decreased, whereas PGE2 increased. Meanwhile, expressions of nephrin, podocin and CD2AP mRNA and protein were dramatically downregulated, activated caspase-3 was increased, and activated PI3K/Akt activity were depressed. Butaprost intervention promoted podocyte proliferation with reduced apoptosis. Conversely, AH6809 intervention led to opposite results (P<0.05). Our findings suggested that EP2 agonist protects podocytes by increasing expression of cAMP, which creates feedback of inhibiting PGE2 expression. This causes the interaction of nephrin, podocin and CD2AP resulting the inhibition of apoptosis induced by activation of the PI3K / Akt signaling pathway. |
