Prostaglandin E2 EP1 receptor enhances TGF‑β1-induced mesangial cell injury

Chen,Xu; Jiang,Daishan; Wang,Jing; Chen,Xiaolan; Xu,Xiaolin; Xi,Peipei; Fan,Yaping; Zhang,Xiaoyan; Guan,Youfei

doi:10.3892/ijmm.2014.1979

Prostaglandin E2 EP1 receptor enhances TGF‑β1-induced mesangial cell injury

Authors:
- Xu Chen
- Daishan Jiang
- Jing Wang
- Xiaolan Chen
- Xiaolin Xu
- Peipei Xi
- Yaping Fan
- Xiaoyan Zhang
- Youfei Guan
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Affiliations: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China, Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China
Published online on: October 24, 2014 https://doi.org/10.3892/ijmm.2014.1979
Pages: 285-293

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Abstract

Increasing evidence indicates that transforming growth factor-β1 (TGF-β1) is a pivotal mediator in the pathogenesis of renal fibrosis. Mesangial cells (MCs) are important for glomerular function under both physiological and pathological conditions. Studies have found that the expression level of prostaglandin E2 (PGE2) in MCs increases under high glucose conditions, that PGE2 affects the proliferation and hypertrophy of MCs mainly through the EP1 pathway, and that the proliferation of MCs and the accumulation of extracellular matrix are the main events leading to glomerular fibrosis. In this study, we investigated the effects and mechanisms of action of the EP1 receptor, which is induced by transforming growth factor (TGF)-β1, on the proliferation of mouse MCs, the accumulation of extracellular matrix and the expression of PGE2 synthase. Primary mouse glomerular MCs were isolated from EP1 receptor-deficient mice (EP1-/- mice, in which the EP1 receptor was knocked down) and wild-type (WT) mice (WT MCs). In our preliminary experiments, we found that cell proliferation, as well as the mRNA and protein expression of cyclin D1, proliferating cell nuclear antigen (PCNA), fibronectin (FN), collagen Ⅰ (ColⅠ), membrane-associated PGE2 synthase-1 (mPGES-1) and cyclooxygenase-2 (COX-2) in the WT MCs were significantly increased following treatment with 10 ng/ml TGF-β1 for 24 h. Compared with the WT MCs, following the knockdown of the EP1 gene, the TGF-β1-induced MC injury was markedly suppressed. The aforementioned changes were notably enhanced following treatment with the EP1 agonist, 17-phenyl trinor PGE2 ethyl amide. Additionally, TGF-β1 induced extracellular signal-regulated kinase (ERK) phosphorylation. We found that the TGF-β1-induced ERK phosphorylation was alleviated by EP1 knockdown and promoted by EP1 expresion. These results suggest that the EP1 receptor plays a role in the proliferation of mouse MCs, in the accumulation of extracellular matrix and in the expression of mPGES-1 induced by TGF-β1. Its mechanisms of action are possibly related to the reinforcement of ERK phosphorylation.

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