Background

The process of wound healing is complex. Increasing evidences have shown that lncRNA MALAT1 is abundant in fibroblasts and may be engaged in wound healing process. Therefore, we explored the mechanism of MALAT1 affecting wound healing.

Methods

The expression levels of MALAT1, miR-141-3p as well as ZNF217 in human fibroblast cells (HFF-1) were quantified by qRT-PCR. HFF-1 proliferation was measured by MTT, while migration was detected by wound healing assay. SMAD2 activation and matrix proteins expression were detected by western blotting. The interaction between miR-141-3p and MALAT1 or ZNF217 was further confirmed using the luciferase reporter gene assay. In vivo wound healing was assessed by full-thickness wound healing model on C57BL/6 mice.

Result

Knockdown of MALAT1 as well as overexpression miR-141-3p remarkably inhibited the proliferation, migration and matrix protein expression in HFF-1 cells. MALAT1 directly targeted and inhibited the expression of miR-141-3p. MiR-141-3p suppressed the activation of TGF-β2/SMAD2 signaling pathway by targeting ZNF217. Knockdown of MALAT1 inhibited wound healing process in mice.

Conclusions

MALAT1 up-regulates ZNF217 expression by targeting miR-141-3p, thus enhances the activity of TGF-β2/SMAD2 signaling pathway and promotes wound healing process. This investigation shed new light on the understanding of the role of MALAT1 in wound healing, and may provide potential target for the diagnosis or therapy of chronic wounds.

中文翻译：

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LncRNA MALAT1 通过调节 miR-141-3p/ZNF217 轴促进伤口愈合

背景

伤口愈合的过程很复杂。越来越多的证据表明，lncRNA MALAT1 在成纤维细胞中含量丰富，可能参与伤口愈合过程。因此，我们探讨了 MALAT1 影响伤口愈合的机制。

方法

通过 qRT-PCR 定量人成纤维细胞 (HFF-1) 中 MALAT1、miR-141-3p 和 ZNF217 的表达水平。通过MTT测量HFF-1增殖，而通过伤口愈合试验检测迁移。通过蛋白质印迹检测SMAD2活化和基质蛋白表达。使用荧光素酶报告基因测定进一步证实了 miR-141-3p 与 MALAT1 或 ZNF217 之间的相互作用。通过 C57BL/6 小鼠的全层伤口愈合模型评估体内伤口愈合情况。

结果

敲低 MALAT1 以及过表达 miR-141-3p 显着抑制 HFF-1 细胞的增殖、迁移和基质蛋白表达。MALAT1 直接靶向并抑制 miR-141-3p 的表达。MiR-141-3p 通过靶向 ZNF217 抑制 TGF-β2/SMAD2 信号通路的激活。MALAT1 的敲低抑制了小鼠的伤口愈合过程。

结论

MALAT1通过靶向miR-141-3p上调ZNF217表达，从而增强TGF-β2/SMAD2信号通路活性，促进伤口愈合过程。该研究为理解MALAT1在伤口愈合中的作用提供了新的思路，并可能为慢性伤口的诊断或治疗提供潜在的靶点。