Involvement of HB-EGF and EGF receptor transactivation in TGF-β–mediated fibronectin expression in mesangial cells

摘要: Involvement of HB-EGF and EGF receptortransactivation in TGF-β–mediated fibronectin expression mesangial cells. Background Gq-coupled receptors are known to transactivate epidermal growth factor receptor (EGFR) via the Ca2+ PKC pathways phosphorylate extracellular signal-regulated kinase (ERK). Methods We studied involvement EGFR transforming factor-β (TGF-β)–mediated (FN) using glomerular Results TGF-β up-regulated FN mRNA accumulation a time- dose-dependent manner, which was completely inhibited by phosphatidylcholine-phospholipase C (PC-PLC) inhibitor inhibitors (calphostin-C staurosporin). The AG1478 abolished expression. ERK inactivation PD98059, p38MAPK SB203580 also showed significant inhibitory effects. Addition neutralizing anti-heparin-binding EGF-like (HB-EGF) antibody, pretreatment with heparin metalloproteinase (MMP) batimastat blocked In cells stably transfected chimera containing alkaline phosphatase (ALP) genes, ALP activity incubation medium rapidly increased (2.1-fold at 0.5 min) reached 3.7-fold increase two minutes, calphostin-C or batimastat. phosphorylated EGFR, PKC- MMP-dependent manner. Smad2 phosphorylation not affected AG1478, did activate Smad2. stability TGF-β. Cycloheximde interfere Conclusions present study demonstrated that processed released PC-PLC-PKC signaling is an intermediate molecule for transactivation, subsequent activation involved transcriptional regulation without requiring new protein synthesis.