EP4 knockdown alleviates glomerulosclerosis through Smad and MAPK pathways in mesangial cells.

EP4 knockdown alleviates glomerulosclerosis through Smad and MAPK pathways in mesangial cells.
Mol Med Rep. 2018 Oct 12;:
Authors: Cao Y, Pan T, Chen X, Wu J, Guo N, Wang B
Abstract
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 wild‑type (WT) mice. Clinical parameters were monitored post‑surgery. At 8 weeks post‑surgery, glomerular fibrosis‑associated indicators were measured by immunohistochemical staining and trichrome staining. In vitro, mesangial cells in different groups (transfected with green fluorescent protein, AD‑EF4 or AD‑CRE) were exposed to transforming growth factor (TGF)‑β1 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 post‑surgery along with less tubule‑interstitial fibrosis. In vivo, the inhibition of extracellular signal‑regulated kinase and P38 phosphorylation ...

Source: Molecular Medicine Reports - October 16, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research