Hypertrophic scar (HTS) is a complicated pathological process induced mainly by burns and wounds, with abnormal proliferation of fibroblasts and the transformation of fibroblasts to myofibroblasts. PAPPA-AS1, a differentially expressed long noncoding RNA (lncRNA) in the HTS tissues, attracted our interests in its potential role and mechanism in the development and process of HTS. In the present study, the regulatory effect of lncRNA PAPPA-AS1 on the Toll-like receptor 4 (TLR4) signal pathway, as well as the molecular mechanism, was investigated. Bioinformatics analysis was utilized to screen the differentially expressed lncRNAs in HTS tissues. PAPPA-AS1 was significantly upregulated in both HTS tissues and hypertrophic scar fibroblast (HTsFb) cells. The expression levels of TLR4, MyD88, TGF-β1, collagen I, collagen III, and α-SMA were greatly elevated in HTsFb cells. By knocking down PAPPA-AS1, the proliferation of HTsFb cells, TLR4, and TGF-β1 signal pathway and the expression of fibrosis markers both in HTsFb cells and HTS tissues were suppressed. It was accompanied by the alleviated pathological state in the HTS tissues, which were significantly reversed by cotransfecting with the pcDNA3.1-TLR4 vector. Positive correlation and interaction were observed between PAPPA-AS1 and TAF15 and between TAF15 and the promoter of TLR4, respectively. In conclusion, lncRNA PAPPA-AS1 might induce the development of HTS by upregulating TLR4 through interacting with TAF15.

中文翻译：

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lncRNA PAPPA-AS1 通过与 TAF15 相互作用上调 TLR4 诱导增生性瘢痕的发展

增生性瘢痕（HTS）是一种以烧伤和创面为主的复杂病理过程，伴有成纤维细胞异常增殖和成纤维细胞向肌成纤维细胞的转化。PAPPA-AS1是一种在高温超导组织中差异表达的长链非编码RNA（lncRNA），它在高温超导的发展和过程中的潜在作用和机制引起了我们的兴趣。本研究探讨了lncRNA PAPPA-AS1对Toll样受体4（TLR4）信号通路的调控作用及其分子机制。利用生物信息学分析筛选 HTS 组织中差异表达的 lncRNA。PAPPA-AS1 在 HTS 组织和肥厚性瘢痕成纤维细胞 (HTsFb) 中均显着上调。TLR4、MyD88、TGF- β的表达水平如图1所示，胶原蛋白I、胶原蛋白III和α- SMA在HTsFb细胞中显着升高。通过敲低 PAPPA-AS1，HTsFb 细胞、TLR4 和 TGF- β1信号通路的增殖以及 HTsFb 细胞和 HTS 组织中纤维化标志物的表达均受到抑制。它伴随着HTS组织中的病理状态减轻，通过与pcDNA3.1-TLR4载体共转染显着逆转。PAPPA-AS1与TAF15之间以及TAF15与TLR4启动子之间分别存在正相关和交互作用。总之，lncRNA PAPPA-AS1可能通过与TAF15相互作用上调TLR4来诱导HTS的发展。