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http://purl.uniprot.org/citations/26032256http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26032256http://www.w3.org/2000/01/rdf-schema#comment"

Aims

bFGF is a potent mitogen of cells associated with fibrosis. Although ERK5 has been reported to play roles in the development of fibrosis, its roles in regulating bFGF-induced fibrotic responses are not understood, especially in lung fibroblasts. The authors investigated the role of ERK5 in bFGF induction of cell proliferation and in induction of PAI-1, a critical regulator of the pathological features of fibrosis, in lung fibroblasts.

Main methods

The role played by ERK5 in bFGF-induced PAI-1 expression was elucidated by perturbing the ERK5 signaling pathway using a specific chemical inhibitor and siRNA of ERK5. The effects of ERK5 signal perturbation on PAI-1 expression were measured at multiple levels by Q-PCR, immunoblotting, ELISA, and reporter gene analysis. The role of MEF2 in bFGF-induced activation of PAI-1 promoter activity via ERK5 was measured using a biotin-labeled DNA pull-down assay, and the effects of ERK5 on the mitogenic effects of bFGF were assessed using a MTT assay.

Key findings

In both primary human lung fibroblast and lung fibroblast cell lines, inhibition of ERK5 blocked bFGF-induced PAI-1 expression at both mRNA and protein levels and inhibited bFGF-induced PAI-1 promoter activity induction by bFGF. Upon stimulation with bFGF, MEF2 directly bound to the consensus sequence of the MEF2 binding site in the PAI-1 promoter. In addition, bFGF-induced PAI-1 up-regulation was inhibited by MEF2 siRNA, and bFGF-induced fibroblast proliferation was blocked by inhibiting ERK5.

Significance

This study reveals a novel role for the ERK5-MEF2 cascade, linking bFGF-induced PAI-1 expression and subsequent mitogenic processes in lung fibroblasts."xsd:string
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http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/author"Kim S."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/author"Lim J.H."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/author"Han J.H."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/author"Choi H.C."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/author"Nam D.H."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/author"Woo C.H."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/author"Hwang A.R."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/name"Life Sci"xsd:string
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http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/title"ERK5 regulates basic fibroblast growth factor-induced type 1 plasminogen activator inhibitor expression and cell proliferation in lung fibroblasts."xsd:string
http://purl.uniprot.org/citations/26032256http://purl.uniprot.org/core/volume"135"xsd:string
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