title: Role of the JAK-STAT pathway in proliferation and differentiation of human hypertrophic scar fibroblasts induced by connective tissue growth factor.
abstract: The aim of this study was to investigate whether the JAK-STAT pathway participates in the processes of proliferation and differentiation induced by connective tissue growth factor (CTGF) in human hypertrophic scar fibroblasts (hHSF). hHSF were grown as primary cultures, then treated with or without CTGF. Western blotting was used to detect JAK1, JAK2, JAK3, TYK2, STAT1, STAT2, STAT3, STAT4, STAT5 and STAT6 protein expression in the hHSF at various time points after stimulation with CTGF. Immunofluorescence and the electrophoretic mobility shift assay (EMSA) were used to identify the interacting signalling molecules and to investigate their activation, respectively. After the signalling molecules of interest were selected, a specific inhibitor (STAT1 ASODN) was used to block the JAK-STAT pathway. The MTT assay was used to detect the proliferation of hHSF, and differentiation was assessed by evaluating changes in α-SMA expression by RT-PCR. Based on the results of Western blotting, immunofluorescence and EMSA, proliferation and differentiation were much higher in hHSF treated with CTGF (p<0.05). After blocking the pathway with STAT1 ASODN, hHSF proliferation was markedly, though not entirely, inhibited, while α-SMA expression was not significantly altered. JAK1 and STAT1 are therefore likely to participate in the proliferation and differentiation of hHSF induced by CTGF. However, though the STAT1 signalling pathway plays a key role in the CTGF-induced proliferation of hHSF, it is not the only pathway controlling this process. JAK1 may be an upstream element of STAT1, and may also participate in the CTGF-induced proliferation of hHSF. These results elucidate the signal transduction mechanism of CTGF-induced hHSF proliferation, and may aid in the development of a novel method for the inhibition of scar fibrosis and contraction.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.forename: Jianyi
authors.initials: J
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Dai
authors.forename: Shirong
authors.initials: S
authors.lastname: Li