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Dysregulation of miR-25-3p in Diabetic Nephropathy and Its Role in Inflammatory Response

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Abstract

To investigate the expression level of miR-25-3p in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), and its effect on proliferation, apoptosis and inflammatory response of mesangial cells cultured with high glucose. Blood samples of all clinical subjects were collected for RT-qPCR analysis to detect serum miR-25-3p levels. Human mesangial cells (HMCs) cultured with high glucose were used to construct DN model in vitro. MTT assay, flow cytometry and ELISA were used to evaluate the effects of miR-25-3p on the proliferation, apoptosis, and inflammatory response of DN cell models. Serum miR-25-3p was decreased in both T2DM group and DN group, but more in DN group. Serum miR-25-3p was positively correlated with eGFR and negatively correlated with UAER. The expression of miR-25-3p was reduced in HMCs induced by high glucose. Transfection of miR-25-3p mimic could significantly up-regulate the miR-25-3p level in HMCs. Besides, high glucose culture resulted in abnormal proliferation of HMCs, reduced apoptotic cells, and increased inflammation. The addition of miR-25-3p mimic significantly inhibited cell proliferation and promoted cell apoptosis and reduced the production of inflammatory factors. The abnormal reduction of serum miR-25-3p in DN indicates that it may be a potential biomarker for clinical diagnosis of DN. In in vitro experiments, miR-25-3p was involved in the progression of DN by regulating cell proliferation, apoptosis, and inflammatory response.

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Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  • Afify AY (2020) A miRNA’s insight into the regenerating heart: a concise descriptive analysis. Heart Fail Rev 25:1047–1061

    Article  CAS  PubMed  Google Scholar 

  • Chamberlain JJ, Rhinehart AS, Shaefer CF Jr, Neuman A (2016) Diagnosis and management of diabetes: synopsis of the 2016 American diabetes association standards of medical care in diabetes. Ann Intern Med 164:542–552

    Article  PubMed  Google Scholar 

  • Cheng Y, Zhang X, Ma F, Sun W, Wang W, Yu J, Shi Y, Cai L, Xu Z (2020) The role of Akt2 in the protective effect of fenofibrate against diabetic nephropathy. Int J Biol Sci 16:553–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Committee of the Japan Diabetes Society on the Diagnostic Criteria of Diabetes M, Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, Ito C, Inagaki N, Iwamoto Y, Kasuga M, Hanafusa T, Haneda M, Ueki K (2010) Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig 1:212–228

    Article  Google Scholar 

  • de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, Uleryk E, Budylowski P, Schunemann H, Beyene J, Anand SS (2015) Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 351:h3978

    Article  PubMed  PubMed Central  Google Scholar 

  • Fu Y, Zhang Y, Wang Z, Wang L, Wei X, Zhang B, Wen Z, Fang H, Pang Q, Yi F (2010) Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. Am J Nephrol 32:581–589

    Article  CAS  PubMed  Google Scholar 

  • Gholaminejad A, Abdul Tehrani H, Gholami Fesharaki M (2018) Identification of candidate microRNA biomarkers in diabetic nephropathy: a meta-analysis of profiling studies. J Nephrol 31:813–831

    Article  CAS  PubMed  Google Scholar 

  • Glovaci D, Fan W, Wong ND (2019) Epidemiology of diabetes mellitus and cardiovascular disease. Curr Cardiol Rep 21:21

    Article  PubMed  Google Scholar 

  • Hansen HP, Tauber-Lassen E, Jensen BR, Parving HH (2002) Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy. Kidney Int 62:220–228

    Article  PubMed  Google Scholar 

  • Kim SR, Kwon SH (2021) Podocytes and microRNA-30/Cx43 axis in diabetic nephropathy. Ann Transl Med 9:828

    Article  PubMed  PubMed Central  Google Scholar 

  • Kolset SO, Reinholt FP, Jenssen T (2012) Diabetic nephropathy and extracellular matrix. J Histochem Cytochem 60:976–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liao X, Zhu Y, Xue C (2022) Diagnostic value of serum cystatin C for diabetic nephropathy: a meta-analysis. BMC Endocr Disord 22:149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin KY, Hsih WH, Lin YB, Wen CY, Chang TJ (2021) Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig 12:1322–1325

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu TX, Rothenberg ME (2018) MicroRNA. J Allergy Clin Immunol 141:1202–1207

    Article  CAS  PubMed  Google Scholar 

  • Mu X, Yang M, Ling P, Wu A, Zhou H, Jiang J (2022) Acylcarnitines: can they be biomarkers of diabetic nephropathy? Diabetes Metab Syndr Obes 15:247–256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muendlein A, Geiger K, Leiherer A, Saely CH, Fraunberger P, Drexel H (2020) Evaluation of the associations between circulating microRNAs and kidney function in coronary angiography patients. Am J Physiol Renal Physiol 318:F315–F321

    Article  CAS  PubMed  Google Scholar 

  • Niu M, Feng Y, Zhang N, Shao T, Zhang H, Wang R, Yao Y, Yao R, Wu Q, Cao J, Liu X, Liu Y, Xu K (2019) High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia. Cancer Cell Int 19:122

    Article  PubMed  PubMed Central  Google Scholar 

  • Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226–230

    Article  CAS  PubMed  Google Scholar 

  • Qin L, Zhang R, Yang S, Chen F, Shi J (2019) Knockdown of ANGPTL-4 inhibits inflammatory response and extracellular matrix accumulation in glomerular mesangial cells cultured under high glucose condition. Artif Cells Nanomed Biotechnol 47:3368–3373

    Article  CAS  PubMed  Google Scholar 

  • Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH (2019) An overview of microRNAs: biology, functions, therapeutics, and analysis methods. J Cell Physiol 234:5451–5465

    Article  CAS  PubMed  Google Scholar 

  • Shaikh H, Bradhurst P, Ma LX, Tan SYC, Egger SJ, Vardy JL (2020) Body weight management in overweight and obese breast cancer survivors. Cochrane Database Syst Rev 12:012110

    Google Scholar 

  • Shantikumar S, Caporali A, Emanueli C (2012) Role of microRNAs in diabetes and its cardiovascular complications. Cardiovasc Res 93:583–593

    Article  CAS  PubMed  Google Scholar 

  • Unwin N, Alberti KG (2006) Chronic non-communicable diseases. Ann Trop Med Parasitol 100:455–464

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Yang Q, Nie Y, Guo H, Zhang F, Zhou X, Yin X (2017) Tetrahydrobiopterin contributes to the proliferation of mesangial cells and accumulation of extracellular matrix in early-stage diabetic nephropathy. J Pharm Pharmacol 69:182–190

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Zhang X, Fang L, Guan Q, Guan L, Li Q (2018) Prevalence, awareness, treatment and control of diabetes mellitus among middle-aged and elderly people in a rural Chinese population: a cross-sectional study. PLoS ONE 13:e0198343

    Article  PubMed  PubMed Central  Google Scholar 

  • Wei J, Wang Z, Han T, Chen J, Ou Y, Wei L, Zhu X, Wang K, Yan Z, Han YP, Zheng X (2023) Extracellular vesicle-mediated intercellular and interorgan crosstalk of pancreatic islet in health and diabetes. Front Endocrinol 14:1170237

    Article  Google Scholar 

  • Xiao J, Luo X, Lin H, Zhang Y, Lu Y, Wang N, Zhang Y, Yang B, Wang Z (2007) MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. J Biol Chem 282:12363–12367

    Article  CAS  PubMed  Google Scholar 

  • Xu JL, Gan XX, Ni J, Shao DC, Shen Y, Miao NJ, Xu D, Zhou L, Zhang W, Lu LM (2018) SND p102 promotes extracellular matrix accumulation and cell proliferation in rat glomerular mesangial cells via the AT1R/ERK/Smad3 pathway. Acta Pharmacol Sin 39:1513–1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M (2010) Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 107:810–817

    Article  CAS  PubMed  Google Scholar 

  • Zha X, Xi X, Fan X, Ma M, Zhang Y, Yang Y (2020) Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8. Aging 12:8137–8150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Long J, Jiang W, Shi Y, He X, Zhou Z, Li Y, Yeung RO, Wang J, Matsushita K, Coresh J, Zhao MH, Wang H (2016) Trends in chronic kidney disease in China. N Engl J Med 375:905–906

    Article  PubMed  Google Scholar 

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by HZC, TGT and DW. The first draft of the manuscript was written by HZC and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Huanzhen Chen.

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The study was conducted with the approval of the Shanghai Jiangong Hospital Medical Ethics Committee and in accordance with the guidelines of the Declaration of Helsinki. Studies were conducted with the approval of the written informed consent of the subjects.

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Chen, H., Tian, T. & Wang, D. Dysregulation of miR-25-3p in Diabetic Nephropathy and Its Role in Inflammatory Response. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10781-x

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