Hypertrophic scar (HS) is a kind of serious pathological scar with no currently effective treatment. HS fibroblasts (HSFs) are the main effector cells for HS formation. Ellagic acid (EA) exerts regulatory effects in some diseases, but its role in HS remains unclear. This study aimed to evaluate the effect of EA on the fibrotic phenotypes of HSFs and to further investigate the downstream signaling mechanism. The cell counting kit-8 (CCK-8) assay was used to perform cytotoxicity and proliferation assays. HSFs migration was assessed using wound healing and transwell assays. HSFs contraction was measured by a collagen lattice contraction assay and detection of α-smooth muscle actin (α-SMA) expression. The levels of mRNA and protein were determined by qPCR and western blotting, respectively. The results showed that EA inhibited the proliferation, migration, and contraction of HSFs and collagen expression in HSFs in a dose-dependent manner. Furthermore, EA not only suppressed the Smad2/3 pathway but also reversed TGF-β1-induced activation of the Smad2/3 pathway and up-regulation of the fibrotic cellular phenotypes in HSFs. These findings demonstrate that EA exerts anti-fibrotic effects on HSFs by blocking the TGF-β1/Smad2/3 pathway, which indicates that EA is a potential therapeutic candidate for treatment of HS.

中文翻译：

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鞣花酸通过抑制 TGF-β1/Smad2/3 通路对增生性瘢痕成纤维细胞发挥抗纤维化作用

肥厚性瘢痕（HS）是一种严重的病理性瘢痕，目前尚无有效治疗方法。HS 成纤维细胞 (HSF) 是 HS 形成的主要效应细胞。鞣花酸 (EA) 在某些疾病中发挥调节作用，但其在 HS 中的作用尚不清楚。本研究旨在评估 EA 对 HSF 纤维化表型的影响，并进一步研究下游信号传导机制。细胞计数试剂盒-8 (CCK-8) 测定用于进行细胞毒性和增殖测定。使用伤口愈合和 transwell 试验评估 HSF 迁移。通过胶原晶格收缩测定和检测 α-平滑肌肌动蛋白 (α-SMA) 表达来测量 HSF 收缩。mRNA 和蛋白质的水平分别通过 qPCR 和蛋白质印迹测定。结果表明，EA抑制了增殖，HSF 的迁移和收缩以及 HSF 中胶原蛋白的表达呈剂量依赖性。此外，EA 不仅抑制 Smad2/3 通路，还逆转 TGF-β1 诱导的 Smad2/3 通路激活和 HSF 中纤维化细胞表型的上调。这些发现表明 EA 通过阻断 TGF-β1/Smad2/3 通路对 HSF 发挥抗纤维化作用，这表明 EA 是治疗 HS 的潜在候选药物。