FOXO1 promotes wound healing through the up-regulation of TGF-β1 and prevention of oxidative stress

被引:174
作者
Ponugoti, Bhaskar [1 ]
Xu, Fanxing [1 ,2 ]
Zhang, Chenying [1 ,3 ]
Tian, Chen [1 ]
Pacios, Sandra [1 ,4 ]
Graves, Dana T. [1 ]
机构
[1] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA
[2] Dalian Univ Technol, Sch Life Sci & Biotechnol, Dalian 116024, Peoples R China
[3] Peking Univ, Sch & Hosp Stomatol, Dept Prevent Dent, Beijing 100081, Peoples R China
[4] Univ Int Catalunya, Sch Dent Med, Sant Cugat Del Valles 08195, Spain
关键词
FORKHEAD TRANSCRIPTION FACTORS; EPIDERMAL-GROWTH-FACTOR; CELL-MIGRATION; EXPRESSION; REPAIR; BETA-1; REEPITHILIALIZATION; ALPHA-V-BETA-6; KERATINOCYTES; HOMEOSTASIS;
D O I
10.1083/jcb.201305074
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Keratinocyte mobilization is a critical aspect of wound re-epithelialization, but the mechanisms that control its precise regulation remain poorly understood. We set out to test the hypothesis that forkhead box O1 (FOXO1) has a negative effect on healing because of its capacity to inhibit proliferation and promote apoptosis. Contrary to expectations, FOXO1 is required for keratinocyte transition to a wound-healing phenotype that involves increased migration and up-regulation of transforming growth factor beta 1 (TGF-beta 1) and its downstream targets, integrin-alpha 3 and -beta 6 and MMP-3 and -9. Furthermore, we show that FOXO1 functions in keratinocytes to reduce oxidative stress, which is necessary to maintain cell migration and prevent cell death in a TGF-beta 1-independent manner. Thus, our studies identify a novel function for FOXO1 in coordinating the response of keratinocytes to wounding through up-regulation of TGF-beta 1 and other factors needed for keratinocyte migration and protection against oxidative stress, which together promote migration and decrease apoptosis.
引用
收藏
页码:327 / 343
页数:17
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