Aberrant expression of long noncoding RNA (lncRNA) H19 and microRNA (miR)‐29b has been implicated in the complications of diabetes mellitus (DM). As a common and important complication of DM, diabetic foot ulcer (DFU) is characterized by high incidence and poor prognosis. Herein, we explored the role of lncRNA H19 in wound healing of DFU. Differentially expressed DM‐related lncRNAs were initially screened by microarray data analysis. DFU models were then induced in DM mouse models. The functional role and interaction of lncRNA H19, miR‐29b and FBN1 in DFU were subsequently determined by examining the proliferation, migration, and apoptosis of fibroblasts after silencing H19, inhibiting or overexpressing miR‐29b and FBN1. According to microarray‐based analysis, lncRNA H19 was upregulated in DM. In the ulcerative edge tissues of DFU, high expression of lncRNA H19 and FBN1 and low expression of miR‐29b were observed. FBN1 was identified to be a target gene of miR‐29b. LncRNA H19 could competitively bind to miR‐29b, and then, inhibited its expression, which consequently upregulating FBN1. Silencing of lncRNA H19 led to inhibited proliferation, migration, and enhanced apoptosis of fibroblasts, accompanied by downregulated FBN1 but upregulated miR‐29b, which diminished the expression of TGF‐β1, Smad3, FN, and Col‐1 and reduced extracellular matrix accumulation. Altogether, upregulation of lncRNA H19 can elevate the expression of FBN1 through competitively binding to miR‐29b, which enhances the proliferation, migration, and inhibits apoptosis of fibroblasts, thus facilitating the wound healing of DFU.

中文翻译：

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长链非编码 RNA H19 作为 miR-29b 海绵促进糖尿病足溃疡伤口愈合

长链非编码 RNA (lncRNA) H19 和微小 RNA (miR)-29b 的异常表达与糖尿病 (DM) 的并发症有关。糖尿病足溃疡(DFU)作为DM常见且重要的并发症，具有发病率高、预后差的特点。在此，我们探讨了 lncRNA H19 在 DFU 伤口愈合中的作用。最初通过微阵列数据分析筛选差异表达的 DM 相关 lncRNA。然后在 DM 小鼠模型中诱导 DFU 模型。随后通过检查沉默 H19、抑制或过表达 miR-29b 和 FBN1 后成纤维细胞的增殖、迁移和凋亡来确定 lncRNA H19、miR-29b 和 FBN1 在 DFU 中的功能作用和相互作用。根据基于微阵列的分析，lncRNA H19 在 DM 中上调。在 DFU 的溃疡边缘组织中，观察到 lncRNA H19 和 FBN1 的高表达和 miR-29b 的低表达。FBN1 被确定为 miR-29b 的靶基因。LncRNA H19 可以与 miR-29b 竞争性结合，然后抑制其表达，从而上调 FBN1。lncRNA H19的沉默导致成纤维细胞增殖、迁移和凋亡增强，同时FBN1下调但miR-29b上调，从而减少TGF-β1、Smad3、FN和Col-1的表达，减少细胞外基质积累。总之，lncRNA H19的上调可以通过与miR-29b竞争性结合来提高FBN1的表达，从而增强成纤维细胞的增殖、迁移和抑制细胞凋亡，从而促进DFU的伤口愈合。FBN1 被确定为 miR-29b 的靶基因。LncRNA H19 可以与 miR-29b 竞争性结合，然后抑制其表达，从而上调 FBN1。lncRNA H19的沉默导致成纤维细胞增殖、迁移和凋亡增强，同时FBN1下调但miR-29b上调，从而减少TGF-β1、Smad3、FN和Col-1的表达，减少细胞外基质积累。总之，lncRNA H19的上调可以通过与miR-29b竞争性结合来提高FBN1的表达，从而增强成纤维细胞的增殖、迁移和抑制细胞凋亡，从而促进DFU的伤口愈合。FBN1 被确定为 miR-29b 的靶基因。LncRNA H19 可以与 miR-29b 竞争性结合，然后抑制其表达，从而上调 FBN1。lncRNA H19的沉默导致成纤维细胞增殖、迁移和凋亡增强，同时FBN1下调但miR-29b上调，从而减少TGF-β1、Smad3、FN和Col-1的表达，减少细胞外基质积累。总之，lncRNA H19的上调可以通过与miR-29b竞争性结合来提高FBN1的表达，从而增强成纤维细胞的增殖、迁移和抑制细胞凋亡，从而促进DFU的伤口愈合。lncRNA H19的沉默导致成纤维细胞增殖、迁移和凋亡增强，同时FBN1下调但miR-29b上调，从而减少TGF-β1、Smad3、FN和Col-1的表达，减少细胞外基质积累。总之，lncRNA H19的上调可以通过与miR-29b竞争性结合来提高FBN1的表达，从而增强成纤维细胞的增殖、迁移和抑制细胞凋亡，从而促进DFU的伤口愈合。lncRNA H19的沉默导致成纤维细胞增殖、迁移和凋亡增强，同时FBN1下调但miR-29b上调，从而减少TGF-β1、Smad3、FN和Col-1的表达，减少细胞外基质积累。总之，lncRNA H19的上调可以通过与miR-29b竞争性结合来提高FBN1的表达，从而增强成纤维细胞的增殖、迁移和抑制细胞凋亡，从而促进DFU的伤口愈合。