Liu Xiao-Qian, Duan Li-Shuang, Chen Yong-Quan, Jin Xiao-Ju, Zhu Na-Na, Zhou Xun, Wei Han-Wei, Yin Lei, Guo Jian-Rong
Department of Anesthesiology, Gongli Hospital, The Second Military Medical University, Shanghai 200135, P.R. China.
Department of Anesthesiology, Yijishan Hospital, Wannan Medical College, Wuhu 241000, P.R. China.
Mol Ther Nucleic Acids. 2019 Sep 6;17:504-515. doi: 10.1016/j.omtn.2019.05.020. Epub 2019 Jun 6.
Impaired wound healing is a debilitating complication of diabetes. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized to be differentially expressed in various diseases. However, its underlying mechanism in diabetes has not been fully understood. Notably, we aim to examine the expression of MALAT1 in diabetic mice and its role in wound healing involving the hypoxia-inducible factor-1α (HIF-1α) signaling pathway with a modified autologous blood preservative solution reported. A mouse model of diabetes was established. MALAT1 was identified to promote the activation of the HIF-1α signaling pathway and to be enriched in autologous blood through modified preservation, which might facilitate the improvement of physiological function of blood cells. Through gain- or loss-of-function approaches, viability of fibroblasts cultured in high glucose, wound healing of mice, and collagen expression in wound areas were enhanced by MALAT1 and HIF-1α. Taken together, the present study demonstrated that the physiological status of mouse blood was effectively improved by modified autologous blood preservation, which exhibited upregulated MALAT1, thereby accelerating the fibroblast activation and wound healing in diabetic mice via the activation of the HIF-1α signaling pathway. The upregulation of MALAT1 activating the HIF-1α signaling pathway provides a novel insight into drug targets against diabetes.
伤口愈合受损是糖尿病的一种使人衰弱的并发症。长链非编码RNA（lncRNA）转移相关肺腺癌转录本1（MALAT1）已被认为在各种疾病中存在差异表达。然而，其在糖尿病中的潜在机制尚未完全阐明。值得注意的是，我们旨在研究MALAT1在糖尿病小鼠中的表达及其在伤口愈合中的作用，该过程涉及缺氧诱导因子-1α（HIF-1α）信号通路，并报告了一种改良的自体血液保存溶液。建立了糖尿病小鼠模型。研究发现，MALAT1通过改良保存促进HIF-1α信号通路的激活，并在自体血液中富集，这可能有助于改善血细胞的生理功能。通过功能获得或缺失方法，MALAT1和HIF-1α增强了高糖培养的成纤维细胞的活力、小鼠的伤口愈合以及伤口区域的胶原蛋白表达。综上所述，本研究表明，改良的自体血液保存有效地改善了小鼠血液的生理状态，其表现为MALAT1上调，从而通过激活HIF-1α信号通路加速糖尿病小鼠的成纤维细胞活化和伤口愈合。MALAT1上调激活HIF-1α信号通路为抗糖尿病药物靶点提供了新的见解。
