Keloids are scars characterized by abnormal proliferation of fibroblasts and overproduction of extracellular matrix components including collagen. We previously showed that LY2109761, a transforming growth factor- (TGF-) β receptor inhibitor, suppressed the secretion of matrix components and slowed the proliferation of fibroblasts derived from human hypertrophic scar tissue. However, the exact mechanism underlying this effect remains unclear. Here, we replicated the above results in keloid-derived fibroblasts and show that LY2109761 promoted apoptosis, decreased the phosphorylation of Smad2 and Smad3, and suppressed TGF-β1. These results suggest that the development and pathogenesis of keloids are positively regulated by the Smad2/3 signaling pathway and the upregulation of TGF-β1 receptors. LY2109761 and other inhibitors of these processes may therefore serve as therapeutic targets to limit excessive scarring after injury.

中文翻译：

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LY2109761 对人瘢痕疙瘩成纤维细胞发育的抑制作用

瘢痕疙瘩是一种疤痕，其特征是成纤维细胞异常增殖和细胞外基质成分（包括胶原蛋白）过度产生。我们之前表明 LY2109761，一种转化生长因子 - (TGF-) β受体抑制剂，抑制基质成分的分泌并减缓源自人类肥厚性瘢痕组织的成纤维细胞的增殖。然而，这种效应背后的确切机制仍不清楚。在这里，我们在瘢痕疙瘩来源的成纤维细胞中重复了上述结果，并表明 LY2109761 促进细胞凋亡，降低 Smad2 和 Smad3 的磷酸化，并抑制 TGF- β1。这些结果表明瘢痕疙瘩的发展和发病机制受到 Smad2 的正调控/3 信号通路和 TGF-的上调β 1 受体。因此，LY2109761 和这些过程的其他抑制剂可作为治疗靶点，以限制损伤后过度瘢痕形成。