Study of Serum microRNA-217 Expression Pattern in Different Stages of Diabetic Kidney Disease – a Cross-sectional Study

Ponnudhali Doraiwamy 1, Lakshmiprabha Prabha Sivalingam 2, Priya K. Dhas 3, Nagarajan Palaniappan 4 *
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1 Department of Biochemistry, Vinayaka Missions’ Kirupananda Variyar Medical College and Hospital, Vinayaka Missions Research Foundation (DU), Salem, Tamil Nadu, India
2 Department of Biochemistry, KMMC Medical College and Hospital, Muttom, Kanyakumari, Tamil Nadu, India
3 Department of Biochemistry, Vinayaka Missions’ Kirupananda Variyar Medical College & Hospital, Vinayaka Missions Research Foundation (DU), Salem, Tamil Nadu, India
4 Department of Nephrology, Govt. Mohankumaramangalam Medical College and Hospital, Salem-1, Tamil Nadu, India
* Corresponding Author
J CLIN MED KAZ, Volume 23, Issue 2, pp. 109-114. https://doi.org/10.23950/jcmk/18054
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Author Contributions: Conceptualization, N.P. and P.D.; methodology, P.D., L.P.S. and P.K.D.; validation, P.D. and P.K.D.; formal analysis, P.D. and L.P.S.; investigation, P.D., L.P.S. and N.P.; resources, N.P.; data curation, P.D. and L.P.S.; writing – original draft preparation, P.D.; writing – review and editing, P.D., L.P.S., P.K.D. and N.P.; visualization, P.D. and P.K.D.; supervision, N.P.; project administration, N.P.; funding acquisition, N/A. All authors have read and agreed to the published version of the manuscript.

Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Artificial Intelligence (AI) Disclosure Statement: The authors declare no AI Tools used for preparation of this work.

ABSTRACT

Background: Diabetic kidney disease (DKD) represents the leading cause of end-stage renal disease worldwide, affecting 30-40% of patients with type 2 diabetes mellitus (T2DM). Some microRNAs (miRNAs), like miRNA-217 are upregulated in Diabetic Kidney Disease (DKD), and known to play a key role in Diabetes Mellitus & its complications. Recent studies have shown miRNA 217 to be involved in the development of DKD,  by promoting renal inflammation, angiogenesis and fibrosis.

Aim and objectives: To assess the miR217 expression levels in DKD patients with differing stages of albuminuria, compared to normoalbuminuric Diabetes mellitus -II patients & to identify its role as a predictive biomarker of DKD.

Methodology: This analytical cross-sectional study recruited 135 participants aged 40-65 years from a Govt medical college Hospital in Tamil Nadu. Participants includedT2DM patients (n=34) & DKD patients & healthy controls(n=35). Fasting serum samples were collected & miRNA-217 extraction and qRT-PCR quantification was done & Fold change was calculated, along with the baseline clinical parameters (age, BMI, HbA1c, lipids, urea, creatinine, eGFR, UACR).
Statistical analyses like Kruskal-Wallis tests, Spearman's correlations & ROC curves were computed using Jamovi software version 2.6.44

Results: Serum miRNA-217 expression was markedly elevated in DKD patients with microalbuminuria (39.36 ± 76.24 fold change) & macroalbuminuria (64.32 ± 109.23 fold change) compared to Diabetes mellitus -II patients with normoalbuminuria (2.29 ± 4.77, P=0.027).MiRNA-217 correlated positively with UACR (ρ=0.472, p<0.001) and was able to discriminate DKD from Diabetes-II, with 59% sensitivity & 90% specificity,  ROC analysis yielded AUC 0.738 (p<0.001).

Conclusion: Serum miRNA-217 exhibits progressive up-regulation in accordance with stages of DKD severity, with moderate diagnostic utility. miRNA-217 could be a potential biomarker for early DKD detection and risk stratification, warranting longitudinal studies in larger populations for further validation and establishment of these findings.
Keywords: microRNA 217, miRNA 217, Diabetic Kidney Disease, DKD, UACR

CITATION

Doraiwamy P, Sivalingam LP, Dhas PK, Palaniappan N. Study of Serum microRNA-217 Expression Pattern in Different Stages of Diabetic Kidney Disease – a Cross-sectional Study. J CLIN MED KAZ. 2026;23(2):109-14. https://doi.org/10.23950/jcmk/18054

REFERENCES

  • Gu HF. Genetic and Epigenetic Studies in Diabetic Kidney Disease. Front Genet. 2019; 10: 507. https://doi.org/10.3389/fgene.2019.00507
  • Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017; 12 (12): 2032-2045. https://doi.org/10.2215/CJN.11491116
  • DeFronzo RA, Reeves WB, Awad AS. Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors. Nat Rev Nephrol. 2021; 17 (5): 319-334. https://doi.org/10.1038/s41581-021-00393-8
  • Paul P, Chakraborty A, Sarkar D, Langthasa M, Rahman M, Bari M, Singha RS, Malakar AK, Chakraborty S. Interplay between miRNAs and human diseases. J Cell Physiol. 2018; 233 (3): 2007-2018. https://doi.org/10.1002/jcp.25854
  • Romakina VV, Zhirov IV, Nasonova SN, Grachev VG, Safronova EM, Tereshchenko SN. Circulating microRNAs as potential biomarkers of myocardial fibrosis in patients with heart failure. Kardiologiia. 2018; (1): 66-71. https://doi.org/10.18087/cardio.2018.1.10083
  • Latini A, Ciccacci C, Novelli G, Borgiani P. Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility. Immunol Res. 2017; 65 (4): 811-827. https://doi.org/10.1007/s12026-017-8937-8
  • Kimura M, Kothari S, Gohir W, Camargo JF, Husain S. MicroRNAs in infectious diseases: potential diagnostic biomarkers and therapeutic targets. Clin Microbiol Rev. 2023; 36 (4): e0001523. https://doi.org/10.1128/cmr.00015-23
  • Samadi M, Aziz SG, Naderi R. The effect of tropisetron on oxidative stress, SIRT1, FOXO3a, and claudin-1 in the renal tissue of STZ-induced diabetic rats. Cell Stress Chaperones. 2021; 26 (1): 217-227. https://doi.org/10.1007/s12192-020-01170-5
  • Shao Y, Ren H, Lv C, Ma X, Wu C, Wang Q. Changes of serum Mir-217 and the correlation with the severity in type 2 diabetes patients with different stages of diabetic kidney disease. Endocrine. 2017; 55 (1): 130-138. https://doi.org/10.1007/s12020-016-1069-4
  • Wong L, Tsang YS, Kenny R, Lyburn M, McMahon LP. MiR-423-5p as Optimal Endogenous Control for Quantification of Circulating MicroRNAs in Patients With CKD. Kidney Int Rep. 2023; 8 (10): 2150-2152. https://doi.org/10.1016/j.ekir.2023.07.018
  • Qureshi R, Sacan A. A novel method for the normalization of microRNA RT-PCR data. BMC Med Genomics. 2013; 6 Suppl 1 (Suppl 1): S14. https://doi.org/10.1186/1755-8794-6-S1-S14
  • Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005; 16 (10): 4623-4635. https://doi.org/10.1091/mbc.e05-01-0033
  • Maeda S, Koya D, Araki SI, Babazono T, Umezono T, Toyoda M, Kawai K, Imanishi M, Fukatsu A, Yasuda M, Kasuga M, Nishio Y, Haneda M. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol. 2011; 15 (3): 381-390. https://doi.org/10.1007/s10157-011-0418-0
  • Tang K, Sun M, Shen J, Zhou B. Transcriptional Coactivator p300 and Silent Information Regulator 1 (SIRT1) Gene Polymorphism Associated with Diabetic Kidney Disease in a Chinese Cohort. Exp Clin Endocrinol Diabetes. 2017; 125 (8): 530-537. https://doi.org/10.1055/s-0043-103966
  • Chuang PY, Xu J, Dai Y, Jia F, Mallipattu SK, Yacoub R, Gu L, Nadkarni GN, Shu L, Klotman PE, He JC. In vivo RNA interference models of inducible and reversible Sirt1 knockdown in kidney cells. Am J Pathol. 2014; 184 (7): 1940-1956. https://doi.org/10.1016/j.ajpath.2014.03.016
  • Schelling JR. Tubular atrophy in the pathogenesis of chronic kidney disease progression. Pediatr Nephrol. 2016; 31 (5): 693-706. https://doi.org/10.1007/s00467-015-3169-4
  • Wang W, Sun W, Cheng Y, Xu Z, Cai L. Role of sirtuin-1 in diabetic nephropathy. J Mol Med (Berl). 2019; 97 (3): 291-309. https://doi.org/10.1007/s00109-019-01743-7
  • Xiao H, Liu Z. Effects of microRNA‑217 on high glucose‑induced inflammation and apoptosis of human retinal pigment epithelial cells (ARPE‑19) and its underlying mechanism. Mol Med Rep. 2019; 20 (6): 5125-5133. https://doi.org/10.3892/mmr.2019.10778
  • Matoba K, Kawanami D, Okada R, Tsukamoto M, Kinoshita J, Ito T, Ishizawa S, Kanazawa Y, Yokota T, Murai N, Matsufuji S, Utsunomiya K. Rho-kinase inhibition prevents the progression of diabetic nephropathy by downregulating hypoxia-inducible factor 1α. Kidney Int. 2013; 84 (3): 545-554. https://doi.org/10.1038/ki.2013.130
  • Shao Y, Lv C, Wu C, Zhou Y, Wang Q. Mir-217 promotes inflammation and fibrosis in high glucose cultured rat glomerular mesangial cells via Sirt1/HIF-1α signaling pathway. Diabetes Metab Res Rev. 2016; 32 (6): 534-543. https://doi.org/10.1002/dmrr.2788
  • Fukami K, Yamagishi S, Ueda S, Okuda S. Novel therapeutic targets for diabetic nephropathy. Endocr Metab Immune Disord Drug Targets. 2007; 7 (2): 83-92. https://doi.org/10.2174/187153007780832118
  • Szostak J, Gorący A, Durys D, Dec P, Modrzejewski A, Pawlik A. The Role of MicroRNA in the Pathogenesis of Diabetic Nephropathy. Int J Mol Sci. 2023; 24 (7): 6214. https://doi.org/10.3390/ijms24076214