Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Faculdade de Medicina, Departamento de Patologia, Universidade de São Paulo, Sao Paulo, Brazil.
Int J Exp Pathol. 2022 Dec;103(6):234-244. doi: 10.1111/iep.12456. Epub 2022 Oct 1.
Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-β. Higher expression of vimentin in comparison to α-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of α-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-β was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role.
纤维化是许多组织和器官受到慢性损伤后的一种常见病理生理反应。尽管瘢痕瘤、硬斑病和局限性硬皮病的病因多种多样，但在这三种疾病的发病机制中都存在纤维化过程，而不仅仅是其他个体临床和组织学的独特特征。在这三种慢性皮肤炎症性疾病的每个病例中，我们都研究了 20 个样本。进行了免疫组织化学研究，以探讨α-平滑肌肌动蛋白（α-SMA）和波形蛋白细胞骨架抗原、CD31、CD34、Ki67、p16；CD105、CD163、CD206 和 FOXP3 抗原；以及中央纤维化细胞因子 TGF-β的存在。在所有三种病变类型中，发现波形蛋白的表达均高于α-SMA。CD31 和 CD34 阳性的血管内皮细胞在网状真皮中均可见。Ki67 在硬皮病中的表达较低且几乎不存在。p16 阳性水平高于 ki67，在瘢痕疙瘩的胶原纤维网中、硬皮病的胶原束中和硬斑病的外肉芽肿层中观察到。在瘢痕疙瘩中，α-平滑肌肌动蛋白阳性细胞和很少的 CD34 阳性细胞的存在可能与较高的 p16 抗原表达有关，p16 抗原表达是细胞衰老的一个指标。在所有病变类型中，FOXP3 的表达均较低。在硬斑病和瘢痕瘤中，CD105 阳性细胞主要存在于与外膜紧密接触的血管周围组织中，而在硬斑病中，这些细胞主要与外肉芽肿层中的胶原沉积有关。我们没有发现 CD163 或 CD206 阳性细胞在纤维化过程中有较高的参与。TGF-β仅在瘢痕疙瘩和硬斑病病变中可见。总之，我们认为波形蛋白是三种研究疾病纤维化过程中的主要肌成纤维细胞通用标志物，而内皮-间充质转化（EndoMT）和间充质干细胞（MSCs）和 M2 巨噬细胞可能不起重要作用。
