caa a22 4500 467934630 CHVBK 20180406152953.0 cr unu---uuuuu 170328e20060201xx s 000 0 eng 10.1007/s00408-005-2560-5 doi (NATIONALLICENCE)springer-10.1007/s00408-005-2560-5 Role of Extracellular Signal-Regulated Kinase, p38 Kinase, and Activator Protein-1 in Transforming Growth Factor- β 1-Induced Alpha Smooth Muscle Actin Expression in Human Fetal Lung Fibroblasts In Vitro [Elektronische Daten] [Yongbin Hu, Jinwu Peng, Deyun Feng, Ling Chu, Xiang Li, Zhongyuan Jin, Zhi Lin, Qingfu Zeng] Myofibroblasts characterized by alpha smooth muscle actin(α-SMA) expression play a key role in pulmonary fibrosis. Transforming growth factor-beta1 (TGF-β1) is likely to be involved in the emergence of myofibroblasts, but the intracellular signal pathways for this process have not been well determined. The aim of the present study was to investigate the role of mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathways in TGF-β1-induced α-SMA expression in human fetal lung fibroblasts (HLF-02). We found that TGF-β1 treatment activated p38 kinase and extracellular signal-regulated kinase (Erk) in HLF-02 cells. The induction of α-SMA by TGF-β1 was suppressed by p38 kinase inhibitor (SB203580) and Erk inhibitor (PD98059). AP-1 inhibitor curcumin also inhibited TGF-β1-induced α-SMA expression. In addition, dominant negative mutant c-Jun (TAM67) downregulated TGF-β1-induced AP-1 transactivation and α-SMA expression. In additional, PD98059 but not SB203580 inhibited the AP-1 DNA binding activity induced by TGF-β1. Based on these findings, we conclude that p38 kinase, Erk, and AP-1 are responsible for the α-SMA expression induced by TGF-β1 in human fetal lung fibroblasts. Erk is involved in inducing α-SMA expression via AP-1 activation. Springer Science+Business Media, Inc., 2006 Alpha smooth muscle actin nationallicence Transforming growth factor-β1 nationallicence Mitogen-activated protein kinase nationallicence Activator protein-1 nationallicence Hu Yongbin Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Peng Jinwu Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Feng Deyun Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Chu Ling Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Li Xiang Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Jin Zhongyuan Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Lin Zhi Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Zeng Qingfu Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut Lung Springer-Verlag; www.springer-ny.com 184/1(2006-02-01), 33-42 0341-2040 184:1<33 2006 184 408 https://doi.org/10.1007/s00408-005-2560-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00408-005-2560-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hu Yongbin Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 700 1- Peng Jinwu Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 700 1- Feng Deyun Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 700 1- Chu Ling Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 700 1- Li Xiang Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 700 1- Jin Zhongyuan Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 700 1- Lin Zhi Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 700 1- Zeng Qingfu Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, 410013, Changsha, China aut NATIONALLICENCE 773 0- Lung Springer-Verlag; www.springer-ny.com 184/1(2006-02-01), 33-42 0341-2040 184:1<33 2006 184 408 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer