TGF-beta 1 induced fibroblast proliferation is mediated by the FGF-2/ERK pathway.
Pulmonary fibrosis, defined as the accumulation of connective tissue in the lungs, is a severe and often fatal form of interstitial lung disease. Transforming growth factor-beta (TGF-beta) is a powerful activator of connective tissue synthesis and fibroblast proliferation in the lung, and a critical paracrine signal for the development of pulmonary fibrosis. To investigate signaling pathways downstream of TGF- beta that contribute to lung fibrosis, TGF- beta stimulation of fibroblasts was replicated by treating NIH3T3 fibroblasts with conditioned medium (CM) from TGF- beta -treated type II alveolar epithelial cells (ATII cells). The data showed that fibroblast growth factor 2 (FGF-2) signaling is responsible for TGF-beta 1 CM-induced fibroblast proliferation, while it does not affect TGF-beta 1 CM-induced fibrotic differentiation. Moreover, fibroblast proliferation and differentiation induced by TGF- beta CM was totally abrogated by pretreatment of NIH3T3 cells with the specific ERK1/2 inhibitor, PD98059. These findings indicate that FGF-2 secreted by alveolar epithelial cells in response to TGF- beta 1 induces fibroblast proliferation and fibrotic activation through the ERK kinase pathway.
Department of Emergency, Shengjing Hospital of China Medical University, Shenyang, China. xiaoli_sj@yeah.net
Li
L
Xiao
Yan
Y
Du
Yang
Y
Shen
Ying
Y
He
Hui
H
Zhao
Zhenhua
Z
Li
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D019899:Paracrine Communication; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2