| Chung CL |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=4.608 ------>paper_class3=2 ------>paper_class2=1 ------>vol=40 ------>confirm_bywho=None ------>insert_bywho=clchung ------>Jurnal_Rank=11.8 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=accept ------>medlineContent= ------>unit=E0400 ------>insert_date=20081127 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=6 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Am J Resp Cell Mol Biol (accepted) ------>paper_name=Dynasore, a dynamin inhibitor, induces PAI-1 expression in MeT-5A human pleural mesothelial cells ------>confirm_date=20091013 ------>tch_id=086034 ------>pmid=18978303 ------>page1=accept ------>fullAbstract=Plasminogen activator inhibitor-1 (PAI-1) is a primary regulator of plasminogen activation that plays an essential role in regulating the physiological thrombotic/fibrinogenic balance. The elevation of PAI-1 expression by human pleural mesothelial cells has been reported to contribute to pleural fibrosis and pleurodesis. In this study, we examined the effects on PAI-1 expression of dynasore, a cell-permeable inhibitor of dynamin, and its mechanisms in a human pleural mesothelial cell line (MeT-5A). The results indicated that dynasore enhanced transforming growth factor (TGF)-beta(1)- and TNF-alpha-induced PAI-1 protein expression in a concentration-dependent manner. Furthermore, dynasore significantly up-regulated PAI-1 protein and its messenger RNA expressions. Interestingly, Smad2/3 activation was induced by TGF-beta(1) but not by dynasore. Among signaling inhibitors, a c-Jun NH(2)-terminal kinase (JNK) inhibitor (SP600125) markedly attenuated dynasore-stimulated PAI-1 protein production. Consistently, dynasore strongly increased JNK phosphorylation. On the other hand, there was no enhancement effect by dynasore on TGF-beta(1)-induced matrix metalloproteinase-2 activation. These findings suggest that dynasore may stimulate PAI-1 protein expression and enhance TGF-beta(1) activity through activation of JNK-mediated signaling in human pleural mesothelial cells. Given the profibrotic effect of dynasore, further in vivo studies may be conducted to evaluate its potential as a pleurodesing agent. ------>tmu_sno=None ------>sno=19965 ------>authors2=Sheu JR ------>authors3=Liu HE ------>authors4=Chang SC ------>authors5=Chou YC ------>authors6=Chen WL, Hsiao G ------>authors6_c= ------>authors=Chung CL ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Dynasore, a dynamin inhibitor, induces PAI-1 expression in MeT-5A human pleural mesothelial cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=12 |