Excessive extracellular matrix deposition, in particular collagen, is an important cause of lung fibrosis. Heat shock protein 47 (HSP47), a collagen-binding protein, plays an important role in the intracellular processing of procollagen. A small molecule that blocks the collagen chaperone function of HSP47 has been reported as an HSP47 inhibitor. The aim of this study was to assess the effect of the HSP47 inhibitor on collagen synthesis and other fibrotic process in vitro. We evaluated collagen expression by western blot, and determined cell viability and migration by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scratch test, respectively, in human and mouse lung fibroblasts. Treatment of lung fibroblasts with HSP47 siRNA decreased collagen type I expression. Similarly, the HSP47 inhibitor decreased collagen type I expression in transforming growth factor beta 1 (TGF-β1)-treated lung fibroblasts in a dose-dependent manner. The inhibitor also decreased the viability and cell migration ability of TGF-β1-treated lung fibroblasts. Overall, we demonstrated that HSP47 is a potential therapeutic target for pulmonary fibrosis. The small molecule HSP47 inhibitor may mediate antifibrotic effects by suppressing the overexpression of collagen, and inhibiting the viability and migration of fibroblasts. Further research is needed to clarify the therapeutic potential of this HSP47 inhibitor for pulmonary fibrosis.

过多的细胞外基质沉积，特别是胶原蛋白，是肺纤维化的重要原因。热休克蛋白 47 (HSP47) 是一种胶原结合蛋白，在原胶原的细胞内加工中起着重要作用。一种阻断 HSP47 胶原蛋白伴侣功能的小分子已被报道为 HSP47 抑制剂。本研究的目的是评估 HSP47 抑制剂对体外胶原合成和其他纤维化过程的影响. 我们通过蛋白质印迹评估了胶原蛋白的表达，并分别通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定和划痕试验确定了人和小鼠肺中的细胞活力和迁移成纤维细胞。用 HSP47 siRNA 处理肺成纤维细胞会降低 I 型胶原蛋白的表达。类似地，HSP47 抑制剂以剂量依赖性方式降低转化生长因子 β1 (TGF-β1) 处理的肺成纤维细胞中 I 型胶原蛋白的表达。该抑制剂还降低了 TGF-β1 处理的肺成纤维细胞的活力和细胞迁移能力。总的来说，我们证明了 HSP47 是肺纤维化的潜在治疗靶点。小分子 HSP47 抑制剂可能通过抑制胶原蛋白的过度表达来介导抗纤维化作用，并抑制成纤维细胞的活力和迁移。需要进一步的研究来阐明这种 HSP47 抑制剂对肺纤维化的治疗潜力。