Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
J Invest Dermatol. 2020 Dec;140(12):2515-2524.e3. doi: 10.1016/j.jid.2020.04.010. Epub 2020 May 11.
Fibroblasts produce collagens and other proteins that form the bulk of the extracellular matrix (ECM) in connective tissues. Emerging data point to functional heterogeneity of fibroblasts. However, the lack of subtype-specific markers hinders our understanding of the different roles of fibroblasts in ECM biology, wound healing, diseases, and aging. We have investigated the utility of the cell surface protein CD26 to identify functionally distinct fibroblast subpopulations in human skin. Using flow cytometry and immunohistology, we found that CD26, in combination with the cell surface glycoprotein CD90, identifies a distinct subpopulation of cells, which express relatively high levels of COL1A1, a hallmark of fibroblasts. Importantly, the population of CD26 fibroblasts is selectively increased after wounding of human skin. These cells account for the majority of COL1A1 expression during the ECM remodeling phase of healing. The proportion of CD26 fibroblasts in the skin of young and aged individuals is similar, indicating that the loss of collagen production during aging does not involve selective reduction of CD26 fibroblasts. In culture, the majority of freshly isolated CD26 fibroblasts gain expression of CD26. Taken together, these data provide a foundation for targeting CD26 fibroblasts to modulate wound healing in human skin.
成纤维细胞产生胶原蛋白和其他蛋白质，这些蛋白质构成结缔组织中细胞外基质 (ECM) 的大部分。新出现的数据表明成纤维细胞具有功能异质性。然而，缺乏亚型特异性标志物阻碍了我们理解成纤维细胞在 ECM 生物学、伤口愈合、疾病和衰老中不同作用。我们研究了细胞表面蛋白 CD26 在鉴定人皮肤中功能不同的成纤维细胞亚群中的效用。通过流式细胞术和免疫组织化学，我们发现 CD26 与细胞表面糖蛋白 CD90 结合，可识别出一个独特的细胞亚群，该亚群表达相对高水平的 COL1A1，这是成纤维细胞的标志。重要的是，在人皮肤受伤后，CD26 成纤维细胞的数量会选择性增加。这些细胞在愈合的 ECM 重塑阶段占 COL1A1 表达的大部分。年轻人和老年人皮肤中 CD26 成纤维细胞的比例相似，表明衰老过程中胶原蛋白产生的丧失不涉及 CD26 成纤维细胞的选择性减少。在培养中，大多数新分离的 CD26 成纤维细胞获得 CD26 的表达。综上所述，这些数据为靶向 CD26 成纤维细胞来调节人皮肤的伤口愈合提供了基础。
