| First Author | Cao Y | Year | 2018 |
| Journal | Mol Med Rep | Volume | 18 |
| Issue | 6 | Pages | 5141-5150 |
| PubMed ID | 30320390 | Mgi Jnum | J:294431 |
| Mgi Id | MGI:6456368 | Doi | 10.3892/mmr.2018.9553 |
| Citation | Cao Y, et al. (2018) EP4 knockdown alleviates glomerulosclerosis through Smad and MAPK pathways in mesangial cells. Mol Med Rep 18(6):5141-5150 |
| abstractText | Prostaglandin E2 has exhibited pleiotropic effects in the regulation of glomerulosclerosis progression through its four receptors. The current study aimed to evaluate the effect of prostaglandin receptor EP4 on mesangial cell proliferation. In vivo, 5/6 nephrectomy was introduced into EP4+/ and wildtype (WT) mice. Clinical parameters were monitored postsurgery. At 8 weeks postsurgery, glomerular fibrosisassociated indicators were measured by immunohistochemical staining and trichrome staining. In vitro, mesangial cells in different groups (transfected with green fluorescent protein, ADEF4 or ADCRE) were exposed to transforming growth factor (TGF)beta1 for 24 h to detect the level of downstream signaling. Corresponding signaling inhibitors were also used to validate the signaling effects. Following surgery, EP4+/ mice presented a higher survival rate and normal urine volume compared with the WT group, and serum creatinine level and 24 h urine protein were lower in the EP4+/ mice. Furthermore, associated profibrotic indicators were identified to have decreased at 8 weeks postsurgery along with less tubuleinterstitial fibrosis. In vivo, the inhibition of extracellular signalregulated kinase and P38 phosphorylation alleviated the accumulation of mesangial matrix, and these signals were enhanced when EP4 was overexpressed. EP4 enhancement aggravated imbalanced mesangial cell proliferation stimulated by TGFbeta1 and GS of mice treated with 5/6 nephrectomy through the Smad and mitogenactivated protein kinase pathways. |
