Department of Burns and Plastic Surgery, The Second Hospital, Shandong University, Jinan, Shandong 250033, China; School of Medicine, Shandong University, Jinan, Shandong 250012, China.
Department of Burns and Plastic Surgery, The Second Hospital, Shandong University, Jinan, Shandong 250033, China; School of Medicine, Shandong University, Jinan, Shandong 250012, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Apr;1870(4):167125. doi: 10.1016/j.bbadis.2024.167125. Epub 2024 Mar 19.
Scarring, a prevalent issue in clinical settings, is characterized by the excessive generation of extracellular matrix within the skin tissue. Among the numerous regulatory factors implicated in fibrosis across various organs, the apelin/APJ axis has emerged as a potential regulator of fibrosis. Given the shared attribute of heightened extracellular matrix production between organ fibrosis and scarring, we hypothesize that the apelin/APJ axis also plays a regulatory role in scar development. In this study, we examined the expression of apelin and APJ in scar tissue, normal skin, and fibroblasts derived from these tissues. We investigated the impact of the hypoxic microenvironment in scars on apelin/APJ expression to identify the transcription factors influencing apelin/APJ expression. Through overexpressing or knocking down apelin/APJ expression, we observed their effects on fibroblast secretion of extracellular matrix proteins. We further validated these effects in animal experiments while exploring the underlying mechanisms. Our findings demonstrated that the apelin/APJ axis is expressed in fibroblasts from keloid, hypertrophic scar, and normal skin. The regulation of apelin/APJ expression by the hypoxic environment in scars plays a significant role in hypertrophic scar and keloid development. This regulation promotes extracellular matrix secretion through upregulation of TGF-β1 expression via the PI3K/Akt/CREB1 pathway.
瘢痕形成是临床中普遍存在的问题，其特征是皮肤组织中细胞外基质的过度生成。在各种器官纤维化中涉及的众多调节因子中，apelin/APJ 轴已成为纤维化的潜在调节剂。鉴于器官纤维化和瘢痕形成之间存在细胞外基质产生增加的共同属性，我们假设 apelin/APJ 轴也在瘢痕形成中发挥调节作用。在这项研究中，我们检测了瘢痕组织、正常皮肤和源自这些组织的成纤维细胞中 apelin 和 APJ 的表达。我们研究了瘢痕组织中缺氧微环境对 apelin/APJ 表达的影响，以确定影响 apelin/APJ 表达的转录因子。通过过表达或敲低 apelin/APJ 的表达，我们观察了它们对成纤维细胞细胞外基质蛋白分泌的影响。我们进一步在动物实验中验证了这些影响，同时探讨了潜在的机制。我们的研究结果表明，apelin/APJ 轴在瘢痕疙瘩、增生性瘢痕和正常皮肤的成纤维细胞中表达。瘢痕组织缺氧环境对 apelin/APJ 表达的调节在增生性瘢痕和瘢痕疙瘩的发生发展中起着重要作用。这种调节通过 PI3K/Akt/CREB1 通路上调 TGF-β1 表达来促进细胞外基质的分泌。
