microRNAs调控糖尿病肾病发展的研究进展

doi:10.3877/cma.j.issn.1674-0785.2021.02.010

随着糖尿病发病率逐年上升，其并发症也愈发受到关注，其中糖尿病肾病（DKD）是由糖尿病引起的慢性肾脏疾病，发病机制复杂，目前暂无特异性的有效治疗手段，且预后差。microRNAs（miRNAs）是近年来新发现的非编码单链小RNA，可通过调控靶基因影响DKD肾组织的病理特征，调节DKD的发生、发展机制。就目前研究来看，某种特异性的miRNA将有望成为早期诊断DKD的分子标志物，且可能成为DKD潜在的治疗靶点。故本文就miRNAs参与调控糖尿病肾病发生、发展的相关研究做一综述。

关键词: 糖尿病肾病, 微小RNAs, 发病机制

As the incidence of diabetes has increased year by year, its complications have also received increasing attention. Diabetic kidney disease (DKD) is a chronic kidney disease caused by diabetes and its pathogenesis is complicated. Currently, there is no specific and effective treatment for DKD, and as a result, its prognosis is poor. MicroRNAs (miRNAs) are non-coding single-stranded small RNAs discovered in recent years, which can affect the pathological characteristics of kidney tissue by regulating target genes, and regulate the occurrence and development of DKD. Based on current research, certain specific miRNAs are expected to become diagnostic biomarkers and therapeutic targets for DKD. Therefore, this article reviews the related research on miRNAs involved in the regulation of the occurrence and development of DKD.

Key words: Diabetic kidney disease, MicroRNA, Pathogenesis

表1 可能参与糖尿病肾病发生发展的miRNAs

作用	microRNAs
促进糖尿病肾病发展	miR-1207-5p、miR-124、miR-125b、miR-126、miR-133b、miR-135a、miR-141、miR-155、miR-181a/d、miR-184、miR-192、miR-199b、miR-let7b-5p 、miR-200b/c、miR-21、miR-214、miR-216a、miR-217、miR-22、miR-27a、miR-29c、miR-34a、miR-370、miR-377、miR-503、miR-770、miR-130b、miR-320c、miR-4490、miR-488、miR-101
抑制糖尿病肾病发展	miR-let7c-5p、miR-192、miR-1915-3p、miR-16、miR-146a、miR-130b、miR-126、miR-200a、miR-23b、miR-25、miR-26a、miR-29家族、miR-30家族、miR-33-5p、miR-346a、miR-374a、miR-424、miR-451、miR-4532、miR-93、miR-124、miR-342、miR-1228-3p、miR-27b-3p、miR-15a-5p

表1 可能参与糖尿病肾病发生发展的miRNAs

作用	microRNAs
促进糖尿病肾病发展	miR-1207-5p、miR-124、miR-125b、miR-126、miR-133b、miR-135a、miR-141、miR-155、miR-181a/d、miR-184、miR-192、miR-199b、miR-let7b-5p 、miR-200b/c、miR-21、miR-214、miR-216a、miR-217、miR-22、miR-27a、miR-29c、miR-34a、miR-370、miR-377、miR-503、miR-770、miR-130b、miR-320c、miR-4490、miR-488、miR-101
抑制糖尿病肾病发展	miR-let7c-5p、miR-192、miR-1915-3p、miR-16、miR-146a、miR-130b、miR-126、miR-200a、miR-23b、miR-25、miR-26a、miR-29家族、miR-30家族、miR-33-5p、miR-346a、miR-374a、miR-424、miR-451、miR-4532、miR-93、miR-124、miR-342、miR-1228-3p、miR-27b-3p、miR-15a-5p

1	Xue R, Gui D, Zheng L, et al. Mechanistic insight and management of diabetic nephropathy: recent progress and future perspective [J]. J Diabetes Res, 2017, 2017: 1839809.
2	Zhang L, Long J, Jiang W, et al. Trends in chronic kidney disease in China [J]. Engl J Med, 2016, 375(9): 905-906.
3	Kato M, Natarajan R. MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets [J]. Ann N Y Acad Sci, 2015, 1353(1): 72-88.
4	Zhang Y, Sun X, Icli B, et al. Emerging roles for MicroRNAs in diabetic microvascular disease: novel targets for therapy [J]. Endocr Rev, 2017, 38(2): 145-168.
5	Lee RC, Feinbaum RL, Ambros V. The C.elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 [J]. Cell, 1993, 75: 843-854.
6	Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans [J]. Nature, 2000, 403(6772): 901-906.
7	Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases [J]. Nat Rev Drug Discov, 2017, 16(3): 203-222.
8	Mori MA, Ludwig RG, Garcia-Martin R, et al. Extracellular miRNAs: from biomarkers to mediators of physiology and disease [J]. Cell Metab, 2019, 30(4): 656-673.
9	Wu L, Wang Q, Guo F, et al. MicroRNA-27a induces mesangial cell injury by targeting of PPARγ, and its in vivo knockdown prevents progression of diabetic nephropathy [J]. Sci Rep, 2016, 6(1): 1-12.
10	Yu FN, Hu ML, Wang XF, et al. Effects of microRNA-370 on mesangial cell proliferation and extracellular matrix accumulation by binding to canopy 1 in a rat model of diabetic nephropathy [J]. J Cell Physiol, 2019, 234(5): 6898-6907.
11	Wang Y, Zheng ZJ, Jia YJ, et al. Role of p53/miR-155-5p/sirt1 loop in renal tubular injury of diabetic kidney disease [J]. J Transl Med, 2018, 16(1): 146-154.
12	Huang YF, Zhang Y, Liu CX, et al. microRNA-125b contributes to high glucose-induced reactive oxygen species generation and apoptosis in HK-2 renal tubular epithelial cells by targeting angiotensin-converting enzyme 2 [J]. Eur Rev Med Pharmacol Sci, 2016, 20(19): 4055.
13	Huang YF, Zhang Y, Liu CX, et al. microRNA-125b contributes to high glucose-induced reactive oxygen species generation and apoptosis in HK-2 renal tubular epithelial cells by targeting angiotensin-converting enzyme2 [J]. Eur Rev Med Pharmacol Sci, 2016, 20(19): 4055-4062.
14	Li D, Lu Z, Jia J, et al. Changes in microRNAs associated with podocytic adhesion damage under mechanical stress [J]. J Renin Angiotensin Aldosterone Syst, 2013, 14(2): 97-102.
15	Milas O, Gadalean F, Vlad A, et al. Deregulated profiles of urinary microRNAs may explain podocyte injury and proximal tubule dysfunction in normoalbuminuric patients with type 2 diabetes mellitus [J]. J Investig Med, 2018, 66(4): 747-754.
16	尹萌萌, 彭晖, 杨婕纶, 等. 微小RNA-124通过抑制rho相关蛋白激酶1激活减轻高糖导致的肾小球内皮细胞损伤 [J]. 中华肾脏病杂志, 2017, 33(1): 30-36.
17	Wang JY, Gao YB, Zhang N, et al. miR-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy [J]. Mol Cell Endocrinol, 2014, 392(1-2): 163-172.
18	Mcclelland AD, Herman-Edelstein M, Komers R, et al. miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7 [J]. Clin Sci (Lond), 2015, 129(12): 1237-1249.
19	Kölling M, Kaucsar T, Schauerte C, et al. Therapeutic miR-21 silencing ameliorates diabetic kidney disease in mice [J]. Mol Ther, 2017, 25(1): 165-180.
20	Pishavar E, Behravan J. miR-126 as a therapeutic agent for diabetes mellitus [J]. Curr Pharm Des, 2017, 23(22): 3309-3314.
21	Fourdinier O, Schepers E, Meuth ML, et al. Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients [J]. Sci Rep, 2019, 9(1): 4477.
22	Cao DW, Jiang CM, Wan C, et al. Upregulation of MiR-126 delays the senescence of human glomerular mesangial cells induced by high glucose via telomere-p53-p21-Rb signaling pathway [J]. Curr Med Sci, 2018, 38(5): 758-764.
23	Barutta F, Bruno G, Matullo G, et al. MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the EURODIAB prospective complications study [J]. Acta Diabetologica, 2016, 54(2): 133-139.
24	Zhang S, Mo Q, Wang X. Oncological role of HMGA2 (Review) [J]. Int J Oncol, 2019, 55(4): 775-788.
25	方晓琳, 杨海波, 李宪, 等. HMGA2基因调控Notch信号通路对高糖诱导的肾小管上皮细胞凋亡的影响 [J]. 中国病理生理杂志, 2019, 35(7): 1261-1267.
26	Liu H, Wang X, Liu S, et al. Effects and mechanism of miR-23b on glucose-mediated epithelial-to-mesenchymal transition in diabetic nephropathy [J]. Int J Biochem Cell Biol, 2016, 70: 149-160.
27	Lv N, Li C, Liu X, et al. miR-34b alleviates high glucose-induced inflammation and apoptosis in human HK-2 cells via IL-6R/JAK2/STAT3 signaling pathway [J]. Med Sci Monit, 2019, 25: 8142-8151.
28	Dasare AP, Gondaliya P, Srivastava A, et al. A therapeutic approach towards microRNA29 family in vascular diabetic complications: A boon or curse? [J]. J Diabetes Metab Disord, 2019, 18(1): 243-254.
29	Lin CL, Lee PH, Hsu YC, et al. MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction [J]. J Am Soc Nephrol, 2014, 25(8): 1698-1709.
30	李凤丽. HDAC4对FOXO1的去乙酰化在糖尿病肾病发病机制中的作用 [D].济南: 山东大学, 2015.
31	Bai X, Geng J, Zhou Z, et al. MicroRNA-130b improves renal tubulointerstitial fibrosis via repression of Snail-induced epithelial-mesenchymal transition in diabetic nephropathy [J]. Hong Kong Med J, 2016, 6(1): 1-16.
32	Lv C, Zhou YH, Wu C, et al. The changes in miR-130b levels in human serum and the correlation with the severity of diabetic nephropathy [J]. Diabetes Metab Res Rev, 2015, 31(7): 717-724.
33	王家芷, 王成, 寿岚. 血清miR-130b与糖尿病肾病患者肾脏损伤及远期预后的相关性研究 [J]. 中国中西医结合肾病杂志, 2019, 20(4): 316-318.
34	Motawi TK, Shehata NI, ElNokeety MM, et al. Potential serum biomarkers for early detection of diabetic nephropathy [J]. Diabetes Res Clin Pract, 2018, 136: 150-158.
35	Ma Y, Shi J, Wang F, et al. MiR-130b increases fibrosis of HMC cells by regulating the TGF-β1 pathway in diabetic nephropathy [J]. J Cell Biochem, 2019, 120(3): 4044-4056.
36	Leuenberger N, Robinson N, Saugy M. Circulating miRNAs: a new generation of anti-doping biomarkers [J]. Anal Bioanal Chem, 2013, 405(30): 9617-9623.

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