长链非编码RNA-n267938调控糖尿病内皮间质转化及其分子机制

Diabetic vascular disease is the main cause of death and disability in patients with diabetes mellitus. Endothelial to mesenchymal transition (EndoMT) is the initial cause of diabetic vascular disease, but the molecular mechanism has not been elucidated. LncRNAs RNA is a kind of RNA with more than 200nt, and its alteration is closely related to the occurrence of many diseases, but whether it is involved in diabetic EndoMT is not clear. Our previous study found that LncRNA-n267938 expression was upregulated in diabetic endothelium, suggesting that they are involved in the occurrence of EndoMT. In this project, we put forward a hypothesis: LncRNA-n267938 regulates the expression of DPP4 via miR-448-3p, and induces diabetic EndoMT, leading to diabetic vascular lesions. This project will use molecular cloning, qRT- PCR, IP and luciferase to study: 1) whether LncRNA-n267938 regulates diabetic EndoMT; 2) The role of LncRNA-n267938/miR-448-3p/DPP4 pathway in regulating diabetic EndoMT; 3) whether LncRNA-n267938 is a new target for the prevention and treatment of diabetic EndoMT. This project will provide new target and insights into the treatment of diabetic vascular disease.

糖尿病血管病是糖尿病患者致残和死亡的最主要原因，而内皮间质转化（EndoMT）是糖尿病血管病变发生的重要因素，但其机制不清。LncRNAs是长度超过200nt的RNA分子，其与多种疾病的发生密切相关。我们前期研究发现LncRNA-n267938在糖尿病内皮中表达上调，并发现沉默LncRNA-n267938可抑制内皮细胞发生EndoMT，提示LncRNA-n267938在糖尿病EndoMT中发挥重要作用，但其分子机制有待揭示。本课题拟运用分子克隆、qRT-PCR、免疫共沉淀、Luciferase等技术研究：1）LncRNA-n267938是否调控了糖尿病EndoMT发生；2）LncRNA-n267938/miR-448-3p/DPP4信号通路在糖尿病EndoMT中的作用；3）以LncRNA-n267938为靶点是否可以防治糖尿病EndoMT。本研究将为糖尿病血管病的防治提供新靶点和和新思路。

糖尿病血管病是糖尿病患者致残和死亡的最主要原因，而内皮间质转化（EndoMT）是糖尿病血管病变发生的重要因素，但其机制不清。miRNAs是长约22个核苷酸的非编码的单链小RNA分子，其与多种疾病的发生密切相关。我们前期研究发现miR-448-3p在糖尿病内皮中表达下调，但其分子机制有待揭示。本课题运用分子克隆、Luciferase、qRT-PCR 和Western blot 等技术研究,发现：miR-448-3p通过TGF-β/Smad信号传导通路调控高糖诱导的内皮间质转化；DPP4是miR-448-3p的靶基因； miR-448-3p/DPP-4与糖尿病内皮间质转化的关系；miR-448-3p成为防治糖尿病内皮间质转化的新靶点。本研究将为糖尿病血管病的防治提供新靶点和新思路。