LncRNAs在糖尿病肾病中的功能及意义研究进展
Progress in the Function and Significance of LncRNAs in Diabetic Nephropathy
DOI: 10.12677/ACM.2022.121107, PDF,    科研立项经费支持
作者: 代丽霞*, 陈新田：西安医学院，陕西 西安；李振江, 朱燕亭#：陕西省人民医院肾病血透中心，陕西 西安
关键词: 糖尿病肾病；LncRNAs；生物标志物；治疗靶点；Diabetic Nephropathy； LncRNAs； Biomarkers； Therapeutic Targets
摘要: 糖尿病肾病是糖尿病重要的微血管并发症，引起持续进展的慢性肾脏损害，导致肾功能衰竭。糖尿病肾病作为慢性肾病患者主要病因及死亡原因，极大地加重了全球健康及经济负担。糖尿病肾病发病机制较为复杂，现有治疗方案效果有限，亟待进一步探索发病机制，以更好地预防、治疗、管理糖尿病肾病。长链非编码RNA参与了许多生理过程，如细胞周期调节、细胞凋亡和存活、肿瘤迁移和代谢等。某些LncRNAs在糖尿病肾病发病机制中发挥重要作用。本文综述了参与糖尿病肾病发病机制、作为生物标志物或在临床应用中作为治疗靶点的LncRNAs。
Abstract: Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus, leading to gradual progress in chronic deterioration of renal function, eventually resulting in the occurrence of kidney failure. DN is the major cause of the high morbidity and mortality of chronic kidney disease (CKD), which significantly aggravates the healthy and economic burden globally. Therefore, it is important to explore the underlying mechanism for prevention and management of DN due to the complicated pathogenesis and limited therapy. Long noncoding RNA (LncRNA), a novel target, is involved in many physiological processes, such as cell cycle regulation, apoptosis, cell survival, tumor migration and metabolism. Furthermore, evidence suggests that LncRNAs play a vital role in DN pathogenesis. This review summarizes LncRNAs, which are involved in the pathogenesis of DN, and used as biomarkers or therapeutic targets of DN in clinical practice.
文章引用：代丽霞, 陈新田, 李振江, 朱燕亭. LncRNAs在糖尿病肾病中的功能及意义研究进展[J]. 临床医学进展, 2022, 12(1): 732-740. https://doi.org/10.12677/ACM.2022.121107

参考文献

[1] Williams, R., Karuranga, S., Malanda, B., et al. (2020) Global and Regional Estimates and Projections of Diabetes-Related Health Expenditure: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice, 162, Article ID: 108072. [Google Scholar] [CrossRef] [PubMed]
[2] 王伟达, 李昭君, 陈园园, 等. LncRNA与慢性肾脏病的研究进展[J]. 药学学报, 2019, 54(11): 1918-1925.
[3] Lin, Y.C., Chang, Y.H., Yang, S.Y., Wu, K.D. and Chu, T.S. (2018) Update of Pathophysiology and Management of Diabetic Kidney Disease. Journal of the Formosan Medical Association, 117, 662-675. [Google Scholar] [CrossRef] [PubMed]
[4] Leti, F. and DiStefano, J.K. (2017) Long Noncoding RNAs as Diagnostic and Therapeutic Targets in Type 2 Diabetes and Related Complications. Genes (Basel), 8, 207. [Google Scholar] [CrossRef] [PubMed]
[5] Uesaka, M., Nishimura, O., Go, Y., Nakashima, K., Agata, K. and Imamura, T. (2014) Bidirectional Promoters Are the Major Source of Gene Activation-Associated Non-Coding RNAs in Mammals. BMC Genomics, 15, Article No. 35. [Google Scholar] [CrossRef] [PubMed]
[6] Mirza, A.H., Kaur, S., Brorsson, C.A. and Pociot, F. (2014) Effects of GWAS-Associated Genetic Variants on LncRNAs within IBD and T1D Candidate Loci. PLoS ONE, 9, e105723. [Google Scholar] [CrossRef] [PubMed]
[7] Ebadi, Z., Moradi, N., Kazemi Fard, T., et al. (2019) Captopril and Spironolactone Can Attenuate Diabetic Nephropathy in Wistar Rats by Targeting microRNA-192 and microRNA-29a/b/c. DNA and Cell Biology, 38, 1134-1142. [Google Scholar] [CrossRef] [PubMed]
[8] Yang, Y., Lv, X., Fan, Q., et al. (2019) Analysis of Circulating LncRNA Expression Profiles in Patients with Diabetes Mellitus and Diabetic Nephropathy: Differential Expression Profile of Circulating LncRNA. Clinical Nephrology, 92, 25-35. [Google Scholar] [CrossRef] 
[9] Alvarez, M.L. and DiStefano, J.K. (2011) Functional Characterization of the Plasmacytoma Variant Translocation 1 Gene (PVT1) in Diabetic Nephropathy. PLoS ONE, 6, e18671. [Google Scholar] [CrossRef] [PubMed]
[10] Qin, B. and Cao, X. (2021) LncRNA PVT1 Regulates High Glucose-Induced Viability, Oxidative Stress, Fibrosis, and Inflammation in Diabetic Nephropathy via miR-325-3p/Snail1 Axis. Diabetes, Metabolic Syndrome and Obesity, 14, 1741-1750. [Google Scholar] [CrossRef] 
[11] Zhong, W., Zeng, J., Xue, J., Du, A. and Xu, Y. (2020) Knockdown of LncRNA PVT1 Alleviates High Glucose-Induced Proliferation and Fibrosis in Human Mesangial Cells by miR-23b-3p/WT1 Axis. Diabetology & Metabolic Syndrome, 12, 33. [Google Scholar] [CrossRef] [PubMed]
[12] Yu, D., Yang, X., Zhu, Y., Xu, F., Zhang, H. and Qiu, Z. (2021) Knockdown of Plasmacytoma Variant Translocation 1 (PVT1) Inhibits High Glucose-Induced Proliferation and Renal Fibrosis in HRMCs by Regulating miR-23b-3p/Early Growth Response Factor 1 (EGR1). Endocrine Journal, 68, 519-529. [Google Scholar] [CrossRef] 
[13] Guan, Y., Kuo, W.L., Stilwell, J.L., et al. (2007) Amplification of PVT1 Contributes to the Pathophysiology of Ovarian and Breast Cancer. Clinical Cancer Research, 13, 5745-5755. [Google Scholar] [CrossRef] 
[14] Liu, D.W., Zhang, J.H., Liu, F.X., et al. (2019) Silencing of Long Noncoding RNA PVT1 Inhibits Podocyte Damage and Apoptosis in Diabetic Nephropathy by Upregulating FOXA1. Experimental & Molecular Medicine, 51, 88. [Google Scholar] [CrossRef] [PubMed]
[15] Yan, B., Tao, Z.F., Li, X.M., Zhang, H., Yao, J. and Jiang, Q. (2014) Aberrant Expression of Long Noncoding RNAs in Early Diabetic Retinopathy. Investigative Ophthalmology & Visual Science, 55, 941-951. [Google Scholar] [CrossRef] [PubMed]
[16] Hu, M., Wang, R., Li, X., et al. (2017) LncRNA MALAT1 Is Dysregulated in Diabetic Nephropathy and Involved in High Glucose-Induced Podocyte Injury via Its Interplay with β-Catenin. Journal of Cellular and Molecular Medicine, 21, 2732-2747. [Google Scholar] [CrossRef] [PubMed]
[17] Gong, Q. and Su, G. (2017) Roles of miRNAs and Long Noncoding RNAs in the Progression of Diabetic Retinopathy. Bioscience Reports, 37, BSR20171157. [Google Scholar] [CrossRef] 
[18] Lelli, A., Nolan, K.A., Santambrogio, S., et al. (2015) Induction of Long Noncoding RNA MALAT1 in Hypoxic Mice. Hypoxia (Auckl.), 3, 45-52. [Google Scholar] [CrossRef] 
[19] Li, X., Zeng, L., Cao, C., et al. (2017) Long Noncoding RNA MALAT1 Regulates Renal Tubular Epithelial Pyroptosis by Modulated miR-23c Targeting of ELAVL1 in Diabetic Nephropathy. Experimental Cell Research, 350, 327-335. [Google Scholar] [CrossRef] [PubMed]
[20] Liu, C., Zhuo, H., Ye, M.Y., Huang, G.X., Fan, M. and Huang, X.Z. (2020) LncRNA MALAT1 Promoted High Glucose-Induced Pyroptosis of Renal Tubular Epithelial Cell by Sponging miR-30c Targeting for NLRP3. The Kaohsiung Journal of Medical Sciences, 36, 682-691. [Google Scholar] [CrossRef] [PubMed]
[21] Feng, Y., Chen, S., Xu, J., et al. (2018) Dysregulation of LncRNAs GM5524 and GM15645 Involved in High-Glucose-Induced Podocyte Apoptosis and Autophagy in Diabetic Nephropathy. Molecular Medicine Reports, 18, 3657-3664. [Google Scholar] [CrossRef] [PubMed]
[22] Qian, X., Tan, J., Liu, L., et al. (2018) MicroRNA-134-5p Promotes High Glucose-Induced Podocyte Apoptosis by Targeting bcl-2. The American Journal of Translational Research, 10, 989-997.
[23] Zhang, X., Song, S. and Luo, H. (2016) Regulation of Podocyte Lesions in Diabetic Nephropathy via miR-34a in the Notch Signaling Pathway. Medicine (Baltimore), 95, e5050. [Google Scholar] [CrossRef] 
[24] Yi, H., Peng, R., Zhang, L.Y., et al. (2017) LincRNA-Gm4419 Knockdown Ameliorates NF-κB/NLRP3 Inflammasome-Mediated Inflammation in Diabetic Nephropathy. Cell Death & Disease, 8, e2583. [Google Scholar] [CrossRef] [PubMed]
[25] Li, H., Wu, P., Sun, D., et al. (2020) LncRNA-Gm4419 Alleviates Renal Damage in Rats with Diabetic Nephropathy through NF-κB Pathway. Panminerva Medica. [Google Scholar] [CrossRef] 
[26] Kato, M., Wang, M., Chen, Z., et al. (2016) An Endoplasmic Reticulum Stress-Regulated LncRNA Hosting a microRNA Megacluster Induces Early Features of Diabetic Nephropathy. Nature Communications, 7, Article No. 12864. [Google Scholar] [CrossRef] [PubMed]
[27] Sun, S.F., Tang, P.M.K., Feng, M., et al. (2018) Novel LncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b. Diabetes, 67, 731-744. [Google Scholar] [CrossRef] [PubMed]
[28] Feng, M., Tang, P.M., Huang, X.R., et al. (2018) TGF-β Mediates Renal Fibrosis via the Smad3-Erbb4-IR Long Noncoding RNA Axis. Molecular Therapy, 26, 148-161. [Google Scholar] [CrossRef] [PubMed]
[29] Li, S.Y. and Susztak, K. (2016) The Long Noncoding RNA Tug1 Connects Metabolic Changes with Kidney Disease in Podocytes. Journal of Clinical Investigation, 126, 4072-4075. [Google Scholar] [CrossRef] 
[30] Long, J., Badal, S.S., Ye, Z., et al. (2016) Long Noncoding RNA Tug1 Regulates Mitochondrial Bioenergetics in Diabetic Nephropathy. Journal of Clinical Investigation, 126, 4205-4218. [Google Scholar] [CrossRef] 
[31] Duan, L.J., Ding, M., Hou, L.J., Cui, Y.T., Li, C.J. and Yu, D.M. (2017) Long Noncoding RNA TUG1 Alleviates Extracellular Matrix Accumulation via Mediating microRNA-377 Targeting of PPARγ in Diabetic Nephropathy. Biochemical and Biophysical Research Communications, 484, 598-604. [Google Scholar] [CrossRef] [PubMed]
[32] Lei, X., Zhang, L., Li, Z. and Ren, J. (2018) Astragaloside IV/LncRNA-TUG1/TRAF5 Signaling Pathway Participates in Podocyte Apoptosis of Diabetic Nephropathy Rats. Drug Design, Development and Therapy, 12, 2785-2793. [Google Scholar] [CrossRef] 
[33] Zang, X.J., Li, L., Du, X., Yang, B. and Mei, C.L. (2019) LncRNA TUG1 Inhibits the Proliferation and Fibrosis of Mesangial Cells in Diabetic Nephropathy via Inhibiting the PI3K/AKT Pathway. European Review for Medical and Pharmacological Sciences, 23, 7519-7525.
[34] Meng, D., Wu, L., Li, Z., et al. (2021) LncRNA TUG1 Ameliorates Diabetic Nephropathy via Inhibition of PU.1/RTN1 Signaling Pathway. Journal of Leukocyte Biology. [Google Scholar] [CrossRef] 
[35] Wang, S., Yi, P., Wang, N., Song, M., Li, W. and Zheng, Y. (2021) LncRNA TUG1/miR-29c-3p/SIRT1 Axis Regulates Endoplasmic Reticulum Stress-Mediated Renal Epithelial Cells Injury in Diabetic Nephropathy Model in Vitro. PLoS ONE, 16, e0252761. [Google Scholar] [CrossRef] [PubMed]
[36] Zhou, L., Xu, D.Y., Sha, W.G., Shen, L., Lu, G.Y. and Yin, X. (2015) Long Non-Coding MIAT Mediates High Glucose-Induced Renal Tubular Epithelial Injury. Biochemical and Biophysical Research Communications, 468, 726-732. [Google Scholar] [CrossRef] [PubMed]
[37] Xiao, L., Xu, X., Zhang, F., et al. (2017) The Mitochondria-Targeted Antioxidant MitoQ Ameliorated Tubular Injury Mediated by Mitophagy in Diabetic Kidney Disease via Nrf2/PINK1. Redox Biology, 11, 297-311. [Google Scholar] [CrossRef] [PubMed]
[38] Ji, T.T., Qi, Y.H., Li, X.Y., et al. (2020) Loss of LncRNA MIAT Ameliorates Proliferation and Fibrosis of Diabetic nephropathy through Reducing E2F3 Expression. Journal of Cellular and Molecular Medicine, 24, 13314-13323. [Google Scholar] [CrossRef] [PubMed]
[39] Dong, Q., Wang, Q., Yan, X., Wang, X., Li, Z. and Zhang, L. (2021) Long Noncoding RNA MIAT Inhibits the Progression of Diabetic Nephropathy and the Activation of NF-κB Pathway in High Glucose-Treated Renal Tubular Epithelial Cells by the miR-182-5p/GPRC5A Axis. Open Medicine (Wars), 16, 1336-1349. [Google Scholar] [CrossRef] [PubMed]
[40] Zhang, M., Zhao, S., Xu, C., et al. (2020) Ablation of LncRNA MIAT Mitigates High Glucose-Stimulated Inflammation and Apoptosis of Podocyte via miR-130a-3p/TLR4 Signaling Axis. Biochemical and Biophysical Research Communications, 533, 429-436. [Google Scholar] [CrossRef] [PubMed]
[41] Wang, M., Wang, S., Yao, D., Yan, Q. and Lu, W. (2016) A Novel Long Non-Coding RNA CYP4B1-PS1-001 Regulates Proliferation and Fibrosis in Diabetic Nephropathy. Molecular and Cellular Endocrinology, 426, 136-145. [Google Scholar] [CrossRef] [PubMed]
[42] Wang, S., Chen, X., Wang, M., et al. (2018) Long Non-Coding RNA CYP4B1-PS1-001 Inhibits Proliferation and Fibrosis in Diabetic Nephropathy by Interacting with Nucleolin. Cellular Physiology and Biochemistry, 49, 2174-2187. [Google Scholar] [CrossRef] [PubMed]
[43] Bai, X., Geng, J., Li, X., et al. (2018) Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy. Antioxidants & Redox Signaling, 29, 355-376. [Google Scholar] [CrossRef] [PubMed]
[44] Zhou, L.J., Yang, D.W., Ou, L.N., Guo, X.R. and Wu, B.L. (2020) Circulating Expression Level of LncRNA Malat1 in Diabetic Kidney Disease Patients and Its Clinical Significance. Journal of Diabetes Research, 2020, Article ID: 4729019. [Google Scholar] [CrossRef] [PubMed]
[45] Petrica, L., Hogea, E., Gadalean, F., et al. (2021) Long Noncoding RNAs May Impact Podocytes and Proximal Tubule Function through Modulating miRNAs Expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients. International Journal of Medical Sciences, 18, 2093-2101. [Google Scholar] [CrossRef] [PubMed]
[46] Wang, L., Su, N., Zhang, Y. and Wang, G. (2018) Clinical Significance of Serum LncRNA Cancer Susceptibility Candidate 2 (CASC2) for Chronic Renal Failure in Patients with Type 2 Diabetes. Medical Science Monitor, 24, 6079-6084. [Google Scholar] [CrossRef] 
[47] Gao, J., Wang, W., Wang, F. and Guo, C. (2018) LncRNA-NR_033515 Promotes Proliferation, Fibrogenesis and Epithelial-to-Mesenchymal Transition by Targeting miR-743b-5p in Diabetic Nephropathy. Biomedicine & Pharmacotherapy, 106, 543-552. [Google Scholar] [CrossRef] [PubMed]
[48] Zhang, R., Li, J., Huang, T. and Wang, X. (2017) Danggui Buxue Tang Suppresses High Glucose-Induced Proliferation and Extracellular Matrix Accumulation of Mesangial Cells via Inhibiting LncRNA PVT1. American Journal of Translational Research, 9, 3732-3740.
[49] 汪佳佳. 小檗碱对糖尿病肾病足细胞保护作用及对长链非编码RNA的初步调节作用研究[D]: [硕士学位论文]. 合肥: 安徽医科大学, 2021.
[50] 周学锋. 糖肾方改善糖尿病肾脏纤维化和氧化应激损伤的机制研究[D]: [博士学位论文]. 北京: 北京中医药大学, 2021.
[51] 林晓, 李健春, 谭睿陟, 文丹, 谢席胜, 王丽. 黄芪三七合剂通过调控Arid2-IR/NF-κB信号轴改善糖尿病肾病小鼠肾炎症反应[J]. 中国实验动物学报, 2020, 28(3): 382-389.
[52] 杜华. 益肾颗粒调控LncRNA MALAT1/mTOR诱导足细胞自噬改善糖尿病肾病的机制研究[D]: [博士学位论文]. 北京: 中国中医科学院, 2020.
[53] Yi, Y., Zhao, Y., Huang, Y. and Wang, D. (2017) A Brief Review of RNA-Protein Interaction Database Resources. Noncoding RNA, 3, 6. [Google Scholar] [CrossRef] [PubMed]

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