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Leduc C., Sobilo L., Toumi H., Mondon P., Lespessailles E., Ossant F., Kurfürst R. and Pichon C.

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

Biochimica Et Biophysica Acta (2016) 1860 (6) 1071-1078 - doi : 10.1016/j.bbagen.2016.02.009

par Frapart - publié le , mis à jour le

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.