Balli Martina, Chui Jonathan Sai-Hong, Athanasouli Paraskevi, Abreu de Oliveira Willy Antoni, El Laithy Youssef, Sampaolesi Maurilio, Lluis Frederic
Department of Development and Regeneration, Stem Cell Institute, KU Leuven, B-3000 Leuven, Belgium.
Stem Cells Int. 2019 Dec 31;2019:6461580. doi: 10.1155/2019/6461580. eCollection 2019.
Impaired wound healing and tissue regeneration have severe consequences on the patient's quality of life. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. Accordingly, we show that increased micrograft-dependent cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies.
伤口愈合和组织再生受损会对患者的生活质量产生严重影响。微移植疗法正成为一种有前景且经济实惠的替代方法，通过增强内源性伤口修复过程来改善皮肤再生。然而，微移植治疗有益效果背后的分子机制在很大程度上仍不清楚。在本研究中，我们确定活性蛋白-1（AP-1）成员Fos相关抗原-1（Fra-1）在细胞外信号调节激酶（ERK）介导的可溶性微移植处理的小鼠成年成纤维细胞和人角质形成细胞模型增强的细胞迁移能力中起核心作用。相应地，我们表明抑制AP-1后，微移植依赖性细胞迁移增加和基质金属蛋白酶活性被消除。此外，可溶性微移植处理导致Fra-1和c-Jun的表达增加和翻译后磷酸化，从而导致主要参与细胞迁移调节的伤口愈合相关基因上调。总体而言，我们的工作为无细胞微移植治疗背后的分子机制提供了见解，这可能有助于伤口修复疗法的未来进展。
