| Ho C |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=1.023 ------>paper_class3=2 ------>paper_class2=1 ------>vol=12 ------>confirm_bywho=hsu0320 ------>insert_bywho=wjhuang ------>Jurnal_Rank=74.5 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=356 ------>medlineContent= ------>unit=G0200 ------>insert_date=20080505 ------>iam=3 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=394 ------>journal_name=Nephrology ------>paper_name=Methylglyoxal-induced Fibronectin gene . Methylglyoxal-induced Fibronectin gene expression through Ras-mediated NADPH oxidase activation in renal mesangial cells ------>confirm_date=20080508 ------>tch_id=096017 ------>pmid=17635749 ------>page1=348 ------>fullAbstract=BACKGROUND: The formation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, is accelerated under diabetic conditions. Although recent studies have suggested that apoptotic cell death is involved in diabetic nephropathy, the precise mechanism of MGO-induced renal fibrosis remains to be elucidated. METHODS: Rat kidney mesangial cells with or without pretreatment with inhibitors, including superoxide dismutase, catalase, L-NAME, diphenylene iodonium, rotenone, allopurinol, PD98059, SB203580 and SP600125 were cultured in medium containing 100 microM MGO. In the MGO-treated cell culture system, fibrosis-related signalling pathway was assessed by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction and western blotting. RESULTS: Expression of fibronectin induced by MGO was highest after 48 h treatment. Superoxide production rapidly increased after 2 h and remained at a high level for 24 h. Scavenging O(2) (-) reversed transforming growth factor beta 1 (TGF-beta1) and fibronectin mRNA level. Pretreatment with diphenylene iodonium significantly suppressed MGO-induced superoxide, TGF-beta1 expression and fibronectin gene expression, indicating that NADPH oxidase is responsible for inducing superoxide formation and subsequently induced renal fibrosis. High MGO rapidly enhanced Ras activation in 1 h and progressively increased cytosolic p38 activation. Additionally, SB203580 pretreatment reduced MGO promotion of fibronectin gene activation suggesting that cytosolic p38 activation might affect MGO-induced renal mesangial fibrosis. Inhibiting Ras activity with manumycin A significantly reduced the promoting effect of MGO on superoxide synthesis, and fibronectin expression. CONCLUSION: Induction of superxoide by Ras via p38 pathway activates fibrotic gene transcription of mesangial cells. Reduction of oxidative stress by scavenging superoxide may offer an alternative strategy for controlling MGO-induced renal fibrosis. ------>tmu_sno=None ------>sno=18375 ------>authors2=Lee PH ------>authors3=Huang WJ ------>authors4=Hsu YC ------>authors5=Lin CL ------>authors6=Wang JY ------>authors6_c= ------>authors=Ho C ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Methylglyoxal-induced fibronectin gene expression through Ras-mediated NADPH oxidase activation in renal mesangial cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2007 ------>submit_flag=None ------>publish_month=1 |