Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus.
Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus.
复制标题
lncRNA-MALAT1在糖尿病内皮细胞功能障碍中的致病作用
DOI：
10.1038/cddis.2014.466
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发表时间：
2014-10-30
影响因子：
9
通讯作者：
Jiang Q
中科院分区：
文献类型：
--
作者：
Liu JY;Yao J;Li XM;Song YC;Wang XQ;Li YJ;Yan B;Jiang Q
长链非编码RNA（lncRNAs）在多种生物过程中具有重要作用。我们先前的研究表明，lncRNA - MALAT1的失调与糖尿病相关微血管疾病——糖尿病视网膜病变（DR）的发病机制有关。然而，MALAT1在视网膜血管重塑中的作用仍不明确。在此我们发现，在链脲佐菌素（STZ）诱导的糖尿病大鼠和db/db小鼠的视网膜中，MALAT1的表达显著上调。体内实验中，MALAT1的敲低可明显改善糖尿病视网膜病变，表现为周细胞丢失、毛细血管变性、微血管渗漏和视网膜炎症的减轻。此外，在体外，MALAT1的敲低可调节视网膜内皮细胞的增殖、迁移和管形成。MALAT1与p38丝裂原活化蛋白激酶（MAPK）信号通路之间的相互作用参与了内皮细胞功能的调节。MALAT1的上调是糖尿病诱导的微血管功能障碍的一个关键致病机制。抑制MALAT1可能成为糖尿病相关微血管并发症抗血管生成治疗的一个潜在靶点。
Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications.