Diabetic non healing wounds often result in significant morbidity and mortality. The number of effective targets to detect these wounds are meagre. Slow lymphangiogenesis is one of the complex processes involved in impaired healing of wounds. Long non coding RNAs (lncRNAs) have been importantly recognized for their role in pathological conditions. Multiple studies highlighting the role of lncRNAs in the regulation of several biological processes and complex diseases. Herein, we investigated the role of lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of diabetic foot ulcer (DFU). We report a significant reduction in the expression of lncRNA MALAT1 in the infected DFU subjects which was positively correlated with the expression of angiogenic factors such as Nrf2, HIF-1α and VEGF. Further, expression of pro-inflammatory markers TNF-α and IL-6 were found to be increased while, the expression of anti-inflammatory marker IL-10 was decreased in infected DFU tissues. Involvement of lncRNA MALAT1 in angiogenesis in EA.hy926 cells was demonstrated by silencing the expression of Nrf2, HIF-1α, and VEGF through interference mediated by MALAT1. In addition, its inflammatory role was demonstrated by decreased expression of TNF-α, IL-6 and not affecting the expression of IL-10. Further, CRISPR-Cas9 knock out of Nrf2 decreased the expression of lncRNA MALAT1, HIF-1α and VEGF which revealed the association of Nrf2 in regulating MALAT1/HIF-1α loop through positive feedback mechanism. Collectively, our results suggested the role of Nrf2 on MALAT1/HIF-1α loop in the regulation of angiogenesis, which could act as a novel target in the treatment of diabetic wounds.

糖尿病性非愈合伤口通常导致显着的发病率和死亡率。检测这些伤口的有效目标数量很少。缓慢的淋巴管生成是伤口愈合受损的复杂过程之一。长链非编码 RNA (lncRNA) 因其在病理状况中的作用而得到重要认可。多项研究强调了 lncRNA 在调节多种生物过程和复杂疾病中的作用。在此，我们研究了 lncRNA 转移相关肺腺癌转录物 1 (MALAT1) 在糖尿病足溃疡 (DFU) 进展中的作用。我们报告感染的 DFU 受试者中 lncRNA MALAT1 的表达显着降低，这与 Nrf2、HIF-1α 和 VEGF 等血管生成因子的表达呈正相关。更远，发现感染的DFU组织中促炎标志物TNF-α和IL-6的表达增加，而抗炎标志物IL-10的表达降低。通过 MALAT1 介导的干扰抑制 Nrf2、HIF-1α 和 VEGF 的表达，证明了 lncRNA MALAT1 参与 EA.hy926 细胞的血管生成。此外，其炎症作用通过降低 TNF-α、IL-6 的表达而不影响 IL-10 的表达来证明。此外，CRISPR-Cas9敲除Nrf2降低了lncRNA MALAT1、HIF-1α和VEGF的表达，揭示了Nrf2通过正反馈机制调节MALAT1/HIF-1α环的关联。总的来说，我们的结果表明 Nrf2 对 MALAT1/HIF-1α 环在调节血管生成中的作用，