New progress of mechanism of action of miRNA-21 in diabetic kidney disease and Chinese medicine intervention

doi:10.11958/20230945

Abstract

Abstract:

Diabetic kidney disease is one of the complications of diabetes, which can progress to end-stage renal disease. In recent years, it has been found that miRNAs have become a research hotspot, with miRNA-21 regulating transforming growth factor β1 (TGF-β1)/Smads, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), Wnt/β-catenin and other signaling pathways to promote the progress of diabetic kidney disease. Studies have showed that traditional Chinese medicine has a regulatory effect on the expression of miRNA-21 and can target miRNA-21 to regulate TGF-β1/Smads, phosphatase and tensin homolog /PI3K/AKT/mammalian target of rapamycin (mTOR), peroxisome proliferator activated receptors and other signal transduction pathways to trigger signal cascade reactions, which intervene in pathological processes such as fibrosis, inflammation, oxidative stress and autophagy. In this article, the role of miRNA-21 in diabetic kidney disease and the intervention of traditional Chinese medicine were summarized, in order to provide some reference for the treatment of diabetic kidney disease and the development of new drugs.

Key words: diabetic nephropathies, Traditional Chinese Drugs, miRNA-21, TGF-β1/Smads, PI3K/AKT

CLC Number:

R259.872

References 50

[1]	ANDERS H J, HUBER T B, ISERMANN B, et al. CKD in diabetes:diabetic kidney disease versus nondiabetic kidney disease[J]. Nat Rev Nephrol, 2018, 14(6):361-377. doi:10.1038/s41581-018-0001-y.
[2]	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]. 中华糖尿病杂志, 2021, 13(4):315-409.
	Diabetes Society of Chinese Medical Association. Guideline for the prevention and treatment of type 2 diabetes mellitus in China(2020 edition)[J]. Chin J Diabetes, 2021, 13(4):315-409. doi:10.3760/cma.j.cn115791-20210221-00095.
[3]	RUIZ-ORTEGA M, RODRIGUES-DIEZ R R, LAVOZ C, et al. Special Issue "Diabetic Nephropathy:Diagnosis,prevention and treatment"[J]. J Clin Med, 2020, 9(3):813. doi:10.3390/jcm9030813.
[4]	SZOSTAK J, GORACY A, DURYS D, et al. The role of microRNA in the pathogenesis of diabetic nephropathy[J]. Int J Mol Sci, 2023, 24(7):6214. doi:10.3390/ijms24076214.
[5]	LIU S, WU W, LIAO J, et al. MicroRNA-21:a critical pathogenic factor of diabetic nephropathy[J]. Front Endocrinol(Lausanne), 2022, 13:895010. doi:10.3389/fendo.2022.895010.
[6]	LU X, FAN Q, XU L, et al. Ursolic acid attenuates diabetic mesangial cell injury through the up-regulation of autophagy via miRNA-21/PTEN/Akt/mTOR suppression[J]. PLoS One, 2015, 10(2):e0117400. doi:10.1371/journal.pone.0117400.
[7]	WU H, KONG L, TAN Y, et al. C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21[J]. Diabetologia, 2016, 59(7):1558-1568. doi:10.1007/s00125-016-3958-8.
[8]	ALSHAMMAR G M, AL-QAHTANI W H, ALFARIS N A, et al. Quercetin prevents cadmium chloride-induced hepatic steatosis and fibrosis by downregulating the transcription of miR-21[J]. Biofactors, 2021, 47(3):489-505. doi:10.1002/biof.1724.
[9]	THOMAS M C. Targeting the pathobiology of diabetic kidney disease[J]. Adv Chronic Kidney Dis, 2021, 28(4):282-289. doi:10.1053/j.ackd.2021.07.001.
[10]	ZHANG X Y, LI Y F, MA H, et al. Regulation of MYB mediated cisplatin resistance of ovarian cancer cells involves miR-21-wnt signaling axis[J]. Sci Rep, 2020, 10(1):6893. doi:10.1038/s41598-020-63396-8.
[11]	TSE J, PIERCE T, CARLI A L E, et al. Onco-miR-21 promotes Stat3-dependent gastric cancer progression[J]. Cancers(Basel), 2022, 14(2):264. doi:10.3390/cancers14020264.
[12]	BI L, HUANG Y, LI J, et al. Pirfenidone attenuates renal tubulointerstitial fibrosis through inhibiting miR-21[J]. Nephron, 2022, 146(1):110-120. doi:10.1159/000519495.
[13]	WANG J Y, GAO Y B, 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. doi:10.1016/j.mce.2014.05.018.
[14]	ZHANG L, LIU Y, WANG X, et al. Curcumin alleviates TGF-β1-induced fibrosis in NRK-49F cells via suppression of miR-21 expression,and regulation of the TGF-β1/smad3 signaling pathway[J]. Journal of Traditional Chinese Medical Sciences, 2020, 7(1):68-74. doi:10.1016/j.jtcms.2020.01.001.
[15]	钟瑜, 韩文伦, 朱芸芸, 等. 纤维化肾小管上皮细胞miRNA-21表达情况研究[J]. 中国生化药物杂志, 2017, 37(3):44-47.
	ZHONG Y, HAN W L, ZHU Y Y, et al. Expression of miRNA-21 in fibrotic tubular epithelial cells[J]. Chinese Journal of Biochemical and Pharmaceuticals, 2017, 37(3):44-47. doi:10.3969/j.issn.1005-1678.2017.03.011.
[16]	LIU L, WANG Y, YAN R, et al. BMP-7 inhibits renal fibrosis in diabetic nephropathy via miR-21 downregulation[J]. Life Sci, 2019, 238:116957. doi:10.1016/j.lfs.2019.116957.
[17]	LUO Q, CAI Z, TU J, et al. Total flavonoids from smilax glabra roxb blocks epithelial-mesenchymal transition and inhibits renal interstitial fibrosis by targeting miR-21/PTEN signaling[J]. J Cell Biochem, 2019, 120(3):3861-3873. doi:10.1002/jcb.27668.
[18]	ZHAO S, LI W, YU W, et al. Exosomal miR-21 from tubular cells contributes to renal fibrosis by activating fibroblasts via targeting PTEN in obstructed kidneys[J]. Theranostics, 2021, 11(18):8660. doi:10.7150/thno.62820.
[19]	刘春雅, 金晶, 李玉芳, 等. miR-21靶向PTEN调节PI3K/AKT通路对狼疮性肾炎患者肾小球系膜细胞增殖及炎性因子分泌的影响[J]. 中国中西医结合肾病杂志, 2021, 22(9):759-764,847.
	LIU C Y, JIN J, LI Y F, et al. Effects of miR-21 targeting PTEN regulating PI3K/AKT pathway on mesangial cell proliferation and secretion of inflammatory factors in patients with lupus nephritis[J]. Chinese Journal of Integrated Traditional and Western Nephrology, 2021, 22(9):759-764,847. doi:10.3969/j.issn.1009-587X.2021.09.004.
[20]	LIU R, GUAN S, GAO Z, et al. Pathological hyperinsulinemia and hyperglycemia in the impaired glucose tolerance stage mediate endothelial dysfunction through miR-21,PTEN/AKT/eNOS,and MARK/ET-1 pathways[J]. Front Endocrinol(Lausanne), 2021, 12:644159. doi:10.3389/fendo.2021.
[21]	WANG S, WANG J, ZHANG Z, et al. Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis[J]. J Nephrol, 2017, 30(4):543-550. doi:10.1007/s40620-017-0405-y.
[22]	FANG Q, QUE T, LIU B, et al. β-ionone inhibits epithelial-mesenchymal transition(EMT)in prostate cancer cells by negatively regulating the Wnt/β-catenin pathway[J]. Front Biosci (Landmark Ed), 2022, 27(12):335. doi:10.31083/j.fbl2712335.
[23]	WANG X, GAO Y, TIAN N, et al. Astragaloside IV improves renal function and fibrosis via inhibition of miR-21-induced podocyte dedifferentiation and mesangial cell activation in diabetic mice[J]. Drug Des Devel Ther, 2018, 12:2431-2442. doi:10.2147/DDDT.S170840.
[24]	LIU X J, HONG Q, WANG Z, et al. MicroRNA21 promotes interstitial fibrosis via targeting DDAH1:a potential role in renal fibrosis[J]. Mol Cell Biochem, 2016, 411:181-189. doi:10.1007/s11010-015-2580-2.
[25]	李梦岚, 徐秀, 谭琴. miRNA-21调控JAK2/STAT3信号通路对IgA肾病模型大鼠肾纤维化的影响[J]. 川北医学院学报, 2020, 35(6):952-956.
	LI M L, XU X, TAN Q. miRNA-21 regulates JAK2/STAT3 signaling pathway and regulates renal fibrosis in IgA nephropathy rats[J]. Journal of North Sichuan Medical College, 2020, 35(6):952-956. doi:10.3969/j.issn.1005-3697.2020.06.03.
[26]	DING X, JING N, SHEN A, et al. MiR-21-5p in macrophage-derived extracellular vesicles affects podocyte pyroptosis in diabetic nephropathy by regulating A20[J]. J Endocrinol Invest, 2021, 44(6):1175-1184. doi:10.1007/s40618-020-01401-7.
[27]	XIANG J, ZHANG H, ZHOU X, et al. Atorvastatin restores PPARα inhibition of lipid metabolism disorders by downregulating miR-21 expression to improve mitochondrial function and alleviate diabetic nephropathy progression[J]. Front Pharmacol, 2022, 13:819787. doi:10.3389/fphar.2022.819787.
[28]	马锋锋, 范增慧. 糖尿病肾病中医病因病机研究进展[J]. 中国中医基础医学杂志, 2022, 28(8):1373-1377.
	MA F F, FAN Z H. Research progress on etiology and pathogenesis of diabetic nephropathy in Chinese Medicine[J]. Chinese Journal of Basic Medicine in Traditional Chinese Medicine, 2022, 28(8):1373-1377. doi:10.19945/j.cnki.issn.1006-3250.2022.08.036.
[29]	MAHJABEEN W, KHAN D A, MIRZA S A. Role of resveratrol supplementation in regulation of glucose hemostasis,inflammation and oxidative stress in patients with diabetes mellitus type 2:a randomized,placebo-controlled trial[J]. Complement Ther Med, 2022, 66:102819. doi:10.1016/j.ctim.2022.102819.
[30]	WANG J, HE F, CHEN L, et al. Resveratrol inhibits pulmonary fibrosis by regulating miR-21 through MAPK/AP-1 pathways[J]. Biomed Pharmacother, 2018, 105:37-44. doi:10.1016/j.biopha.2018.05.104.
[31]	YAN B, CHENG L, JIANG Z, et al. Resveratrol inhibits ROS-promoted activation and glycolysis of pancreatic stellate cells via suppression of miR-21[J]. Oxid Med Cell Longev, 2018, 2018:1346958. doi:10.1155/2018/1346958.
[32]	齐宝宁, 熊永爱, 潘艳芳, 等. 大黄素调控miR-21介导细胞自噬减轻糖尿病肾病小鼠肾脏氧化性损伤机制研究[J]. 天然产物研究与开发, 2020, 32(12):2012-2019.
	QI B N, XIONG Y A, PAN Y F, et al. Study on the mechanism of emodin alleviating oxidative damage of mice diabetic nephropathy by regulating miR-21-mediated autophagy[J]. Natural Product Research and Development, 2020, 32(12):2012-2019. doi:10.16333/j.1001-6880.2020.12.004.
[33]	乔青燕, 戴宾宾, 战晓丽, 等. 大黄素联合碳酸氢钠通过抑制miR-21减轻糖尿病肾病蛋白尿的作用及机制研究[J]. 中国中西医结合肾病杂志, 2022, 23(11):957-962,1036.
	QIAO Q Y, DAI B B, ZHAN X L, et al. Effect and mechanism of emodin combined with sodium bicarbonate on reducing proteinuria in diabetic nephropathy by inhibiting miR-21[J]. Chinese Journal of Integrated Traditional and Western Nephrology, 2022, 23(11):957-962,1036. doi:10.3969/j.issn.1009-587X.2022.11.005.
[34]	CUI X, SUN X, LU F, et al. Baicalein represses TGF-β1-induced fibroblast differentiation through the inhibition of miR-21[J]. Toxicol Appl Pharmacol, 2018, 358:35-42. doi:10.1016/j.taap.2018.09.007.
[35]	段海政, 白琳, 白雅, 等. 黄芩苷减轻HFLS-RA合成细胞外基质的分子机制研究[J]. 时珍国医国药, 2019, 30(6):1299-1302.
	DUAN H Z, BAI L, BAI Y, et al. Study on the molecular mechanism of baicalin on alleviating synthesis of extracellular matrix of HFLS-RA[J]. Lishizhen Medicine and Materia Medica Research, 2019, 30(6):1299-1302. doi:10.3969/j.issn.1008-0805.2019.06.006.
[36]	LIU Y R, CHEN J J, DAI M. Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release[J]. Acta Pharmacol Sin, 2014, 35(4):483-488. doi:10.1038/aps.2013.190.
[37]	LI J, GU H. Paeonol suppresses lipid formation and promotes lipid degradation in adipocytes[J]. Exp Ther Med, 2022, 23(1):78. doi:10.3892/etm.2021.11001.
[38]	YANG D, TAN S, YANG Z, et al. Dihydromyricetin attenuates TNF-α-induced endothelial dysfunction through miR-21-mediated DDAH1/ADMA/NO signal pathway[J]. Biomed Res Int, 2018, 2018:1047810. doi:10.1155/2018/1047810.
[39]	ALMOHAWES Z N, EL-KOTT A, MORSY K, et al. Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats[J]. Arch Physiol Biochem, 2022:1-18. doi:10.1080/13813455.2021.2024578.
[40]	CAO Y, HU J, SUI J, et al. Quercetin is able to alleviate TGF-β-induced fibrosis in renal tubular epithelial cells by suppressing miR-21[J]. Exp Ther Med, 2018, 16(3):2442-2448. doi:10.3892/etm.2018.6489.
[41]	徐雪梅, 田春雨, 喇孝瑾, 等. 十子代平方对糖尿病大鼠肾脏TGF-β1、PTEN及血浆miRNA-21表达的影响[J]. 中药材, 2017, 40(6):1443-1447.
	XU X M, TIAN C Y, LA X J, et al. Effects of Shizi Daiping prescription on expression of TGF-β1,PTEN and plasma miRNA-21 in diabetic rats[J]. Journal of Chinese Medicinal Materials, 2017, 40(6):1443-1447. doi:10.13863/j.issn1001-4454.2017.06.045.
[42]	TIAN C, WANG Y, CHANG H, et al. Spleen-kidney supplementing formula alleviates renal fibrosis in diabetic rats via TGF-β1-miR-21-PTEN signaling pathway[J]. Evid Based Complement Alternat Med, 2018, 2018:3824357. doi:10.1155/2018/3824357.
[43]	宋丽丽, 王佳宝, 付晓. 糖克煎剂经miR-21/Tgfb1/Smad信号转导延缓糖尿病肾病肾脏纤维化[J]. 中药药理与临床, 2018, 34(1):135-139.
	SONG L L, WANG J B, FU X. Anti-fibrosis effect of Tangke apozem on DN rats via reglulating miR-21/Tgfb1/Smad signal[J]. Pharmacology and Clinics of Chinese Materia Medica, 2018, 34(1):135-139. doi:10.13412/j.cnki.zyyl.2018.01.033.
[44]	陈洪民, 潘艳伶, 伏红颖, 等. 糖通饮对糖尿病肾病大鼠肾脏纤维化的延缓作用[J]. 中成药, 2023, 45(9):2860-2866.
	CHEN H M, PAN Y L, FU H Y, et al. Access to Tangtong drink to delay effect of diabetic nephropathy rats renal fibrosis[J]. Chinese Traditional Patent Medicine, 2023, 45(9):2860-2866. doi:10.3969/j.issn.1001-1528.2023.09.010.
[45]	吕嘉苇, 庄楷, 蒋希羽, 等. 益气活血固肾颗粒对db/db小鼠肾脏的保护作用及对smad3介导miRNA-21、miRNA-29s表达的影响[J]. 中成药, 2021, 43(5):1170-1179.
	LV J W, ZHUANG K, JIANG X Y, et al. Protective effects of Yiqi Huoxue Gushen Granules on db/db mice and smad3-mediated miRNA-21 and miRNA-29s expressions[J]. Chinese Traditional Patent Medicine, 2021, 43(5):1170-1179. doi:10.3969/j.issn.1001-1528.2021.05.011.
[46]	叶太生, 向楠, 姚琼, 等. 当归补血汤干预miRNA-21调控自噬保护早期糖尿病肾病大鼠肾功能的研究[J]. 时珍国医国药, 2019, 30(2):282-286.
	YE T S, XIANG N, YAO Q, et al. Effect of Danggui Buxue decoction on regulation of autophagy by miRNA-21 to protect renal function in early diabetic nephropathy rats[J]. Lishizhen Medicine and Materia Medica Research, 2019, 30(2):282-286. doi:10.3969/j.issn.1008-0805.2019.02.008.
[47]	WANG Q L, TAO Y Y, XIE H D, et al. Fuzheng Huayu recipe,a traditional Chinese compound herbal medicine,attenuates renal interstitial fibrosis via targeting the miR-21/PTEN/AKT axis[J]. J Integr Med, 2020, 18(6):505-513. doi:10.1016/j.joim.2020.08.006.
[48]	谭秦湘, 陈国姿, 陈思诺, 等. 肾康颗粒对CKD患者TGF-β1、miR-21表达及肾功能的影响[J]. 中国中西医结合肾病杂志, 2018, 19(5):391-394.
	TAN Q X, CHEN G Z, CHEN S N, et al. Effects of Shenkang granule on expression of TGF-β1,miR-21 and renal function in patients with chronic kidney disease[J]. Chinese Journal of Integrated Traditional and Western Nephrology, 2018, 19(5):391-394. doi:10.3969/j.issn.1009-587X.2018.05.006.
[49]	何小泉, 苏保林. 左归丸对老年糖尿病肾病患者外周血miRNA-21表达影响及临床疗效研究[J]. 辽宁中医杂志, 2020, 47(3):124-127.
	HE X Q, SU B L. Study on effect of Zuogui Pill in treatment of diabetic nephropathy patients and its influence on expression of microRNA-21 in peripheral blood[J]. Liaoning Journal of Traditional Chinese Medicine, 2020, 47(3):124-127. doi:10.13192/j.issn.1000-1719.2020.03.038.
[50]	李晓玥, 程军, 俞仲贤, 等. 荆防当归补血汤对早期糖尿病肾病临床疗效、氧化应激状态及肾功能的影响研究[J]. 中华中医药学刊, 2022, 40(6):200-204.
	LI X Y, CHENG J, YU Z X, et al. Effect of Jingfang Danggui Buxue Decoction on clinical curative effect,oxidative stress state and renal function in patients with early diabetic nephropathy[J]. Chinese Archives of Traditional Chinese Medicine, 2022, 40(6):200-204. doi:10.13193/j.issn.1673-7717.2022.06.046.