Department of Surgery, Albany Medical College, Albany, NY 12208, USA; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
Matrix Biol. 2024 Dec;134:175-183. doi: 10.1016/j.matbio.2024.11.002. Epub 2024 Nov 2.
Integrins are cellular transmembrane receptors that physically connect the cytoskeleton with the extracellular matrix. As such, they are positioned to mediate cellular responses to microenvironmental cues. Importantly, integrins also regulate their own microenvironment through secreted factors, also known as the integrin-mediated secretome. Epidermal integrins, or integrins expressed by keratinocytes of the skin epidermis, regulate the cutaneous microenvironment through the contribution of matrix components, via proteolytic matrix remodeling, or by mediating factors like cytokines and growth factors that can promote support for nearby but distinct cells of the stroma, such as immune cells, endothelial cells, and fibroblasts. This role for integrins is enhanced during both pathological and repair tissue remodeling processes, such as tumor growth and progression and wound healing. This review will discuss examples of how the epithelial integrin-mediated secretome can regulate the tissue microenvironment. Although different epithelial integrins in various contexts will be explored, emphasis will be given to epidermal integrins that regulate the secretome during wound healing and cutaneous tumor progression. Epidermal integrin α3β1 is of particular focus as well, since this integrin has been revealed as a key regulator of the keratinocyte secretome.
整合素是细胞的跨膜受体，它将细胞骨架与细胞外基质物理连接起来。因此，它们处于介导细胞对微环境信号做出反应的位置。重要的是，整合素还通过分泌因子（也称为整合素介导的分泌组）来调节自身的微环境。表皮整合素，或皮肤表皮角朊细胞表达的整合素，通过基质成分的贡献、通过蛋白水解基质重塑，或通过介导细胞因子和生长因子等可以促进支持附近但不同的基质细胞，如免疫细胞、内皮细胞和成纤维细胞，来调节皮肤的微环境。在病理性和修复性组织重塑过程中，如肿瘤生长和进展以及伤口愈合，整合素的这种作用得到增强。本文将讨论上皮整合素介导的分泌组如何调节组织微环境的例子。虽然将探讨不同背景下的不同上皮整合素，但重点将放在调节伤口愈合和皮肤肿瘤进展过程中分泌组的表皮整合素上。表皮整合素α3β1 特别值得关注，因为该整合素已被揭示为角蛋白细胞分泌组的关键调节因子。
