1. Role of the prostaglandin E2/E-prostanoid 2 receptor signalling pathway in TGFβ-induced mice mesangial cell damage
- Author
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Yu‑Yin Xu, Jianhua Wu, Ya‑Ping Fan, Na‑Na Li, and Xiaolan Chen
- Subjects
BP, blood pressure ,medicine.medical_treatment ,lcsh:Life ,lcsh:QR1-502 ,CCK, cholecystokinin ,Gene Expression ,Biochemistry ,p38 Mitogen-Activated Protein Kinases ,lcsh:Microbiology ,DMEM, Dulbecco’s modified Eagle’s medium ,chemistry.chemical_compound ,Transforming Growth Factor beta ,CRE, CREB, cAMP responsive element binding protein ,Cyclic AMP ,Cyclin D1 ,Prostaglandin E2 ,Phosphorylation ,Prostaglandin E1 ,Cyclic AMP Response Element-Binding Protein ,Extracellular Signal-Regulated MAP Kinases ,MOI, multiplicity of infection ,Cells, Cultured ,Prostaglandin-E Synthases ,Mesangial cell ,ERK1/2 ,Reverse Transcriptase Polymerase Chain Reaction ,adenovirus ,Cell biology ,ECM, extracellular matrix ,Intramolecular Oxidoreductases ,MC, mesangial cell ,GAPDH, glyceraldehyde-3-phosphate dehydrogenase ,JNK, c-Jun N-terminal kinase ,Mesangial Cells ,lipids (amino acids, peptides, and proteins) ,RNA Interference ,PGE2 ,Signal transduction ,medicine.drug ,Prostaglandin E ,Signal Transduction ,endocrine system ,TGFβ1, transforming growth factor-β1 ,Prostaglandin E2 receptor ,Blotting, Western ,Primary Cell Culture ,Biophysics ,RT–PCR, reverse transcription–PCR ,mPGES-1, membrane associated prostaglandin E1 ,S6 ,Biology ,ERK, extracellular-signal-regulated kinase ,PGES, prostaglandin E2 synthase ,Collagen Type I ,Dinoprostone ,CTGF, connective tissue growth factor ,FBS, fetal bovine serum ,medicine ,PGE2, prostaglandin E2 ,Animals ,EP2 ,COX2, cyclooxygenase-2 ,Protein kinase A ,Molecular Biology ,FN, fibronectin ,Col I, collagen type I ,Cell Proliferation ,Original Paper ,TGFβ1 ,CKD, chronic kidney disease ,Connective Tissue Growth Factor ,Cell Biology ,Receptors, Prostaglandin E, EP2 Subtype ,Molecular biology ,CTGF ,Mice, Inbred C57BL ,lcsh:QH501-531 ,chemistry ,siRNA, small interfering RNA ,Cyclooxygenase 2 ,siRNA ,EP2, E-prostanoid 2 ,PKA, protein kinase A ,MAPK, mitogen-activated protein kinase - Abstract
The prostaglandin E2 receptor, EP2 (E-prostanoid 2), plays an important role in mice glomerular MCs (mesangial cells) damage induced by TGFβ1 (transforming growth factor-β1); however, the molecular mechanisms for this remain unknown. The present study examined the role of the EP2 signalling pathway in TGFβ1-induced MCs proliferation, ECM (extracellular matrix) accumulation and expression of PGES (prostaglandin E2 synthase). We generated primary mice MCs. Results showed MCs proliferation promoted by TGFβ1 were increased; however, the production of cAMP and PGE2 (prostaglandin E2) was decreased. EP2 deficiency in these MCs augmented FN (fibronectin), Col I (collagen type I), COX2 (cyclooxygenase-2), mPGES-1 (membrane-associated prostaglandin E1), CTGF (connective tissue growth factor) and CyclinD1 expression stimulated by TGFβ1. Silencing of EP2 also strengthened TGFβ1-induced p38MAPK (mitogen-activated protein kinase), ERK1/2 (extracellular-signal-regulated kinase 1/2) and CREB1 (cAMP responsive element-binding protein 1) phosphorylation. In contrast, Adenovirus-mediated EP2 overexpression reversed the effects of EP2-siRNA (small interfering RNA). Collectively, the investigation indicates that EP2 may block p38MAPK, ERK1/2 and CREB1 phosphorylation via activation of cAMP production and stimulation of PGE2 through EP2 receptors which prevent TGFβ1-induced MCs damage. Our findings also suggest that pharmacological targeting of EP2 receptors may provide new inroads to antagonize the damage induced by TGFβ1.
- Published
- 2014