METTL3调控miR-126介导TGF-β/Smad信号通路影响糖尿病肾病的机制研究

doi:10.3969/j.issn.1006-6233.2024.03.05

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摘要 目的:建立糖尿病肾病(Diabetes Kidney Disease,DKD)大鼠模型,探讨METTL3调控糖尿病肾病的作用机制。方法:将SD大鼠适应性喂养7d后,按照随机数字法分为4组,正常对照组(Control组)、糖尿病肾病模型组(DKD组)、糖尿病肾病模型+METTL3干扰对照组(DKD+NC组)和糖尿病肾病模型+METTL3干扰组(DKD+siMETTL3组),每组8只。造模结束后收集大鼠血液标本及肾脏组织,采用全自动生化分析仪分析空腹血糖(Fasting blood glucose,FBG)、尿素氮(Blood urea nitrogen,BUN)、24h尿蛋白 (Uridine triphosphate,UTP)的表达水平,RT-qPCR法检测miR-126的基因表达,ELISA检测TGF-β1的表达,Western blotting检测METTL3、smad2、smad3、smad7的蛋白水平。结果: 与Control组相比,DKD组的FBG、BUN、UTP、TGF-β1、METTL3、smad2、smad3显著升高(P<0.05),体质量、miR-126、smad7显著降低(P<0.05);与DKD组比较,DKD+siMETTL3组的FBG、BUN、UTP、TGF-β1、METTL3、smad2、smad3显著降低(P<0.05),体质量、miR-126、smad7显著升高(P<0.05)。结论:METTL3可以通过调控miR-126及TGF-β/smad通路,介导DKD的进展。

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	张静
	任荣
	帕提古丽·阿斯讨拜

关键词 ： miR-126, 糖尿病肾病, 甲基转移酶样3, TGF-β/smad信号通路

Abstract：Objective: To establish a rat model of diabetic kidney disease (DKD) and explore the mechanism by which METTL3 regulates DKD.Methods: After 7 days of adaptive feeding, SD rats were randomly divided into four groups: normal control group (Control group), DKD model group (DKD group), DKD model + METTL3 interference control group (DKD+NC group), and DKD model + METTL3 interference group (DKD+siMETTL3 group), with 8 rats in each group. After modeling, blood specimens and kidney tissues were collected, and levels of fasting blood glucose (FBG), blood urea nitrogen (BUN), 24-hour urine protein (UTP), gene expression of miR-126 using RT-qPCR, expression of TGF-β1 using ELISA, and protein levels of METTL3, smad2, smad3, and smad7 using Western blotting were analyzed by a fully automatic biochemical analyzer. Results: Compared to the control group, the DKD group showed significant increases in FBG, BUN, UTP, TGF-β1, METTL3, smad2, and smad3 (P<0.05), and significant decreases in body weight, miR-126, and smad7 (P<0.05). When compared to the DKD group, the DKD+siMETTL3 group exhibited significant decreases in FBG, BUN, UTP, TGF-β1, METTL3, smad2, and smad3 (P<0.05), and significant increases in body weight, miR-126, and smad7 (P<0.05). Conclusion: METTL3 can mediate the progression of DKD by regulating miR-126 and TGF-β/smad pathway.

Key words： miR-126 Diabetes kidney disease Methyltransferase-like 3 TGF-β/Smad signaling pathway

基金资助:2021年新疆维吾尔自治区创新环境(人才、基地)建设专项(自然科学基金计划-基金项目),(编号:2021D01C433)

通讯作者: 帕提古丽·阿斯讨拜

引用本文:

张静, 任荣, 帕提古丽·阿斯讨拜. METTL3调控miR-126介导TGF-β/Smad信号通路影响糖尿病肾病的机制研究[J]. 河北医学, 2024, 30(3): 377-380.
ZHANG Jing, REN Rong, Patiguli·ASITANBAI. Mechanistic Study on the Regulation of Diabetes Kidney Disease by METTL3 through the miR-126-Mediated TGF-β/Smad Signaling Pathway. HeBei Med, 2024, 30(3): 377-380.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.03.05 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I3/377

[1] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2020年版)[J].中华糖尿病杂,2021,13(4):315-409.
[2] Tuttle KR,Agarwal R,Alpers CE,et al.Molecular mechanisms and therapeutic targets for diabetic kidney disease[J].Kidney Int,2022,102(2):248-260.
[3] 汪霞,张娜.m6A甲基化:糖尿病及其并发症的关键驱动因素[J].河北医科大学学报,2022,43(10):1215-1219.
[4] 吴佳晋,钟晨,李大伟,等.甲基转移酶3调控pri-miR-21甲基化修饰在糖尿病肾病肾脏纤维化中的作用[J].上海交通大学学报(医学版),2023,43(1):1-7.
[5] Yu J,Shen L,Liu Y,et al.The m6A methyltransferase METTL3 cooperates with demethylase ALKBH5 to regulate osteogenic differentiation through NF-κB signaling[J].Mol Cell Biochem,2020,463(1-2):203-210.
[6] 张静,张洁,莫颖,等.METTL3/miR-126调控TGF-β1/smad2对高糖诱导的肾小管上皮细胞增殖的影响[J].广西医科大学学报,2022,39(3):456-461.
[7] Jiang L,Liu X,Hu X,et al.METTL3-mediated m6A modification of TIMP2 mRNA promotes podocyte injury in diabetic nephropathy[J].Mol Ther,2022,30(3):1721-1740.
[8] Sun W,Li Y,Ma D,et al.ALKBH5 promotes lung fibroblast activation and silica-induced pulmonary fibrosis through miR-320a-3p and FOXM1[J].Cell Mol Biol Lett,2022,27(1):26.
[9] 袁瑾,赵灿,张渭涛.依普利酮通过靶向微小 RNA192和微小 RNA-29a/b/c减轻糖尿病肾病模型大鼠肾损伤机制研究[J].陕西医学杂志,2022,51(3):293-297,302.
[10] 胡滨滨,张明.非编码RNA的m6A修饰及其在肿瘤中的研究进展[J].中国癌症防治杂志,2021,13(4):430-435.
[11] 李昌金,郭志福,黄松群.m6A甲基化调节非编码RNA在心血管疾病中的作用[J].生命的化学,2022,42(7):1248-1254
[12] 潘保朝,李函舟,张辉,等.中医药调控TGF-β1/Smad信号通路治疗糖尿病肾病的研究进展[J].中国实验方剂学杂志,2022,28(23):237-249.