Shen Congcong, Sun Linlin, Zhu Ningwen, Qi Fazhi
Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Department of Biochemistry and Molecular Biology, Basic Medical College of Fudan University, Shanghai 200032, P.R. China.
Int J Mol Med. 2017 Apr;39(4):949-959. doi: 10.3892/ijmm.2017.2911. Epub 2017 Mar 7.
The commercial use of epidermal growth factor (EGF) is extensive and has been shown to be effective for skin wound healing in clinical practice. There is evidence to indicate that the topical administration of EGF significantly accelerates re-epithelialization by promoting keratinocyte mitogenesis and migration following acute injury; however, the mechanisms involved remain to be elucidated. Thus, in this study, we focused on Kindlin-1, a four-point-one, ezrin, radixin, moesin (FERM)-domain-containing adaptor protein, and report its contribution to EGF-induced re-epithelialization in skin wound healing. In tissue samples, the expression of Kindlin-1 was induced upon EGF treatment compared to that in the natural healing group. In immortalized human keratinocytes (HaCaT cells), we further proved that Kindlin-1 was necessary for mediating EGF-induced activation signals, including integrin β1 activation, focal adhesion kinase (FAK) phosphorylation and actin re-organization, which finally led to enhanced cell proliferation and migration. These results indicate that Kindlin-1 is essential in EGF-induced re-epithelialization in skin wound healing and provide additional rationale for the clinical application of EGF in the treatment of acute wounds.
表皮生长因子（EGF）的商业用途广泛，并且在临床实践中已被证明对皮肤伤口愈合有效。有证据表明，局部应用EGF可通过促进急性损伤后角质形成细胞的有丝分裂和迁移，显著加速再上皮化；然而，其中涉及的机制仍有待阐明。因此，在本研究中，我们聚焦于Kindlin-1，一种含四点一蛋白、埃兹蛋白、根蛋白、膜突蛋白（FERM）结构域的衔接蛋白，并报告其在皮肤伤口愈合中对EGF诱导的再上皮化的作用。在组织样本中，与自然愈合组相比，EGF处理后Kindlin-1的表达被诱导。在永生化人角质形成细胞（HaCaT细胞）中，我们进一步证明Kindlin-1是介导EGF诱导的激活信号所必需的，这些信号包括整合素β1激活、粘着斑激酶（FAK）磷酸化和肌动蛋白重组，最终导致细胞增殖和迁移增强。这些结果表明Kindlin-1在皮肤伤口愈合中EGF诱导的再上皮化过程中至关重要，并为EGF在急性伤口治疗中的临床应用提供了额外的理论依据。
