RAB31介导TGF-β/Smad通路促进增生性瘢痕形成的作用机制研究
Study on the Mechanism of RAB31-Mediated TGF-β/Smad Pathway Promoting Hypertrophic Scar Formation
摘要: 目的：探讨RAB31在增生性瘢痕(hypertrophic scar, HS)组织中的表达特征及其通过调控TGF-β/Smad信号通路对人真皮成纤维细胞(human dermal fibroblasts, HDFs)生物学功能的影响。方法：基于GEO数据库中HS相关转录组数据集(GSE158395, GSE188952)进行差异基因筛选，并与TGF-β通路基因取交集；收集临床HS及正常皮肤组织，采用qPCR和Western Blot验证RAB31的表达；构建siRNA干扰体系，在人真皮成纤维细胞中敲减RAB31，通过CCK-8法检测细胞增殖，流式细胞术分析细胞凋亡，Transwell实验评估细胞迁移能力；进一步利用Western Blot检测纤维化标志物(Collagen I, α-SMA)及TGF-β/Smad通路关键蛋白(Smad2/3, p-Smad2/3)的表达变化。结果：RAB31在HS组织中mRNA和蛋白水平均显著升高(P < 0.05, P < 0.001)；干扰RAB31可显著抑制TGF-β1诱导的HDFs增殖与迁移(P < 0.01)，促进细胞凋亡(P < 0.001)，并下调Collagen I、α-SMA及p-Smad2/3蛋白表达(P < 0.05)，而对总Smad2/3蛋白无显著影响。结论：RAB31在增生性瘢痕中异常高表达，并通过激活TGF-β/Smad通路促进成纤维细胞增殖、迁移及纤维化蛋白合成，抑制其凋亡，提示RAB31可能作为HS潜在的治疗靶点。
Abstract: Objective: Investigating the expression characteristics of RAB31 in hypertrophic scar (HS) tissue and its impact on the biological functions of human dermal fibroblasts (HDFs) via regulation of the TGF-β/Smad signaling pathway. Methods: Differential gene screening was performed based on HS-related transcriptomic datasets (GSE158395, GSE188952) from the GEO database, and the results were intersected with TGF-β pathway genes. Clinical HS and normal skin tissue samples were collected, and RAB31 expression was validated using qPCR and Western Blot. An siRNA interference system was constructed to knock down RAB31 in HDFs. Cell proliferation was assessed by CCK-8 assay, apoptosis was analyzed by flow cytometry, and cell migration capacity was evaluated using the Transwell assay. Furthermore, Western Blot was employed to detect changes in the expression of fibrosis markers (Collagen I, α-SMA) and key proteins of the TGF-β/Smad pathway (Smad2/3, p-Smad2/3). Results: RAB31 was significantly upregulated at both mRNA and protein levels in HS tissues (P < 0.05, P < 0.001). Knockdown of RAB31 significantly inhibited TGF-β1-induced proliferation and migration of HDFs (P < 0.01), promoted cell apoptosis (P < 0.001), and downregulated the expression of Collagen I, α-SMA, and p-Smad2/3 proteins (P < 0.05), while showing no significant effect on total Smad2/3 protein levels. Conclusion: RAB31 is aberrantly highly expressed in hypertrophic scars and promotes fibroblast proliferation, migration, fibrosis-related protein synthesis, and inhibits apoptosis by activating the TGF-β/Smad pathway. This suggests that RAB31 may serve as a potential therapeutic target for HS.
文章引用：潘一坤, 曹东升. RAB31介导TGF-β/Smad通路促进增生性瘢痕形成的作用机制研究[J]. 临床医学进展, 2026, 16(3): 2535-2544. https://doi.org/10.12677/acm.2026.1631053

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