Role of the prostaglandin E2/E-prostanoid 2 receptor signalling pathway in TGFβ-induced mice mesangial cell damage
| Autor: | Yu‑Yin Xu, Jianhua Wu, Ya‑Ping Fan, Na‑Na Li, Xiaolan Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
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 |
| Zdroj: | Bioscience Reports Bioscience Reports, Vol 34, Iss 6, p e00159 (2014) |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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