Chitturi Pratyusha, Leask Andrew
College of Dentistry, University of Saskatchewan, 105 Wiggins Road, Saskatoon, SK, Canada.
College of Dentistry, University of Saskatchewan, 105 Wiggins Road, Saskatoon, SK, Canada.
Matrix Biol. 2024 Apr;128:31-38. doi: 10.1016/j.matbio.2024.02.009. Epub 2024 Feb 28.
The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes external pathogens and disseminates sensory signals emanating from the local microenvironment. Dermal connective tissue is comprised of a collagen-rich extracellular matrix (ECM) that is produced by connective tissue fibroblasts resident within the dermis. When wounded, a tissue repair program is induced whereby fibroblasts, in response to alterations in the microenvironment, produce new ECM components, resulting in the formation of a scar. Failure to terminate the normal tissue repair program causes fibrotic conditions including: hypertrophic scars, keloids, and the systemic autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc). Histological and single-cell RNA sequencing (scRNAseq) studies have revealed that fibroblasts are heterogeneous and highly plastic. Understanding how this diversity contributes to dermal homeostasis, wounding, fibrosis, and cancer may ultimately result in novel anti-fibrotic therapies and personalized medicine. This review summarizes studies supporting this concept.
皮肤是最大的哺乳动物器官，由位于表皮下方并支撑表皮的真皮结缔组织层组成，它作为一种保护屏障，可排除外部病原体并传播来自局部微环境的感觉信号。真皮结缔组织由富含胶原蛋白的细胞外基质（ECM）组成，该基质由真皮内的结缔组织成纤维细胞产生。受伤时，会诱导组织修复程序，成纤维细胞会响应微环境的变化而产生新的ECM成分，从而形成疤痕。未能终止正常的组织修复程序会导致纤维化病症，包括：肥厚性瘢痕、瘢痕疙瘩和全身性自身免疫性结缔组织病硬皮病（系统性硬化症，SSc）。组织学和单细胞RNA测序（scRNAseq）研究表明，成纤维细胞具有异质性且高度可塑性。了解这种多样性如何促进皮肤稳态、伤口愈合、纤维化和癌症，最终可能会带来新的抗纤维化疗法和个性化医疗。本综述总结了支持这一概念的研究。
