Arciniegas Enrique, Carrillo Luz Marina, Rojas Héctor, Ramírez Richard, Chopite Marina
Institute of Biomedicine, Central University of Venezuela, Caracas, Venezuela.
Autonomous Service Institute of Biomedicine, Caracas, Venezuela.
Am J Dermatopathol. 2019 Mar;41(3):193-204. doi: 10.1097/DAD.0000000000001284.
Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules. Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3). Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered. Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells. We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening. We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids. We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
瘢痕疙瘩在组织病理学上被定义为一种炎症性疾病，其特征是存在大量成纤维细胞、异常血管生成、促炎免疫细胞数量增加、细胞增殖不受控制，以及细胞外基质（ECM）分子沉积加剧和紊乱。重要的是，许多这些ECM分子显示N-和O-连接聚糖残基，被认为是半乳糖凝集素-1（Gal-1）和半乳糖凝集素-3（Gal-3）的潜在靶点。然而，尚未考虑Gal-1和Gal-3在瘢痕疙瘩组织中的存在和定位以及它们与一些结合伴侣的相互作用。在这里，我们表明，在瘢痕疙瘩的真皮增厚中，多功能蛋白聚糖、多配体蛋白聚糖-1、纤连蛋白、血小板反应蛋白-1、腱生蛋白C、CD44、整合素β1和N-钙黏蛋白在靠近免疫细胞浸润、附着于胶原束、围绕微血管以及一些免疫细胞的细长成纤维细胞中免疫定位。我们还表明，Gal-1和Gal-3存在于真皮增厚的一些成纤维细胞、免疫细胞和内皮细胞的细胞质中以及沿细胞膜分布。我们认为，Gal-1和Gal-3与成纤维细胞和免疫细胞产生的一些ECM分子协同作用，抵消瘢痕疙瘩中的炎症反应。我们还提出，Gal-1和Gal-3通过其结合伴侣可能在成纤维细胞、免疫细胞、内皮细胞的细胞表面以及细胞外空间形成超分子结构，这可能影响成纤维细胞的形态、黏附、增殖、迁移和存活以及炎症反应。
