TGF-beta-induced early gene-1 overexpression promotes oxidative stress protection and actin cytoskeleton rearrangement in human skin fibroblasts

Abstract : BACKGROUND: Transforming growth factor beta inducible early gene-1 (TIEG-1), a member of the Kruppel-like factor, was identified as a primary response gene for TGF-beta. The role of TIEG-1 in skin repair has been mainly addressed in vivo on TIEG-1 null mice model and the mechanism remains unexplored. METHODS: We investigated the modulation of TIEG-1 expression in normal human skin fibroblasts by either down-expressing or overexpressing the gene. We evaluated reactive oxygen species production and the cell viability of treated cells. The effect of TIEG-1 overexpression was monitored by wound healing assay and immunofluorescence staining of actin fibers organization and alpha-smooth muscle actin (alpha-SMA). Western blots were carried out to identify the level of expression or phosphorylation of key proteins such as cofilin, Rho GTPases, and p38 mitogen-activated protein kinase (p38 MAPK). RESULTS: TIEG-1 down-regulation had a deleterious effect on the cell viability. It was significantly reduced (65+/-5%) and exposure to ultraviolet further increased this effect (47+/-3%). By contrast, cells overexpressing TIEG-1 had a reduced reactive oxygen species production (75%) compared to control and mock-transfected cells. This overexpression also resulted in formation of actin stress fibers and increased alpha-SMA expression and an enhanced wound healing feature. RhoB GTPase was upregulated and phosphorylation of cofilin and p38 MAPK was observed. CONCLUSION: TIEG-1 overexpression in normal human skin fibroblasts results in improved resistance to oxidative stress, myofibroblast-like conversion that involved RhoB signaling pathway with cofilin and p38 MAPK proteins activation. GENERAL SIGNIFICANCE: This study enlightens the role of TIEG-1 role in skin biology.
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Submitted on : Friday, December 2, 2016 - 5:01:46 PM
Last modification on : Thursday, August 29, 2019 - 3:48:02 PM

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Chloe Leduc, Lauren Sobilo, Hechmi Toumi, Philippe Mondon, Eric Lespessailles, et al.. TGF-beta-induced early gene-1 overexpression promotes oxidative stress protection and actin cytoskeleton rearrangement in human skin fibroblasts. Biochimica et Biophysica Acta:Biomembranes, Elsevier, 2016, 1860 (6), pp.1071 - 1078. ⟨10.1016/j.bbagen.2016.02.009⟩. ⟨hal-01407918⟩

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