ILK-PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast

被引:70
作者
Li, Gang [1 ]
Li, Ye-Yang [1 ]
Sun, Jing-En [1 ]
Lin, Wei-hua [1 ]
Zhou, Ri-xing [1 ]
机构
[1] Jinan Univ, Clin Coll 1, Guangzhou Red Cross Hosp, Dept Burns & Plast Surg, Guangzhou 510220, Guangdong, Peoples R China
关键词
INTEGRIN-LINKED KINASE; GLYCOGEN-SYNTHASE KINASE; ONLY PROTEIN PINCH; KAPPA-B PATHWAYS; CELL-MIGRATION; MESENCHYMAL TRANSITION; COLLAGEN LATTICE; GROWTH; CANCER; PROLIFERATION;
D O I
10.1038/labinvest.2016.48
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The interactions between fibroblasts and the extracellular matrix in wound contraction are mainly mediated via integrin signaling. Integrin-linked kinase (ILK) is a key mediator in integrin signal transduction. We investigated the role of ILK in cutaneous wound contraction. We found that ILK was involved in cutaneous wound healing in rats, and ILK and PI3K/AKT inhibitors inhibited wound contraction and re-epithelialization, consequently delaying wound healing in vivo. Further, using in vitro studies, we demonstrated that ILK and PI3K/AKT inhibitors suppressed the contraction of fibroblast populated collagen lattices, inhibited fibroblast migration, and interrupted the effect of TGF-beta(1) on promoting alpha smooth muscle actin (alpha-SMA) expression in fibroblasts. When ILK expression was directly blocked by ILK small interfering RNA transfection, the migration and alpha-SMA expression of normal dermal fibroblasts were significantly suppressed as well. The data suggest that the ILK-PI3K/AKT signaling pathway mediates cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblasts.
引用
收藏
页码:741 / 751
页数:11
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