THE PRO-INFLAMMATORY ROLE OF MICRORNA-29b IN DIABETIC NEPHROPATHY

Authors

  • NAWAL KHINTEEL JABBAR Department of Chemistry, College of Science, University of AL-Qadisiyah, AL-Diwaniyah, Iraq.
  • ANWARA JASIB THAABAN ALMZAIEL Department of Medical Chemistry, College of Medicine, University of AL-Qadisiyah, AL-Diwaniyah, Iraq.
  • FERDOUS ABASS JABER Department of Medical Chemistry, College of Medicine, University of AL-Qadisiyah, AL-Diwaniyah, Iraq.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i10.34766

Keywords:

Diabetic nephropathy, Inflammation, miRNA, Oxidative stress, Apoptosis

Abstract

Objectives: The objective of the study was to investigate the expression pattern of microRNA-29b (miRNA-29b) in patients with diabetic nephropathy (DN) compared to Type 2 diabetes mellitus (T2DM) and healthy subjects.

Methods: Blood samples were obtained from 30 patients with DN, 30 patients with T2DM and 30 healthy subjects as controls. Serum reactive oxygen species (ROS) and interleukine-10 (IL-10) level were measured by enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction was employed to screen the expression of serum miRNA-29b and anti-apoptotic B-cell lymphoma 2 (Bcl-2).

Results: The results showed a significant increase in ROS levels (p<0.05) in DN group compared with T2DM and control groups. IL-10 levels were significantly increased compared to other groups (p<0.05). The gene expression of miRNA-29b was significantly increased with downregulation of Bcl-2 (p<0.05) in DN compared to T2DM and control groups (p<0.05).

Conclusions: The study suggested that miRNA-29b expression is involved in the pathogenesis of DN. Hyperglycemia induced oxidative stress-mediated apoptosis, and an increase in expression of pro-inflammatory miRNA-29b exerts anti-protective effect by upregulating target genes related to inflammation and apoptosis, taken together, the results identify the regulatory role of miRNA-29b in DN.

Downloads

Download data is not yet available.

References

Groop PH, Thomas MC, Moran JL, Wadèn J, Thorn LM, Mäkinen VP, et al. The presence and severity of chronic kidney disease predicts all-cause mortality in Type 1 diabetes. Diabetes 2009;58:1651-8.

Tervaert TW, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB, et al. Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 2010;21:556-63.

Mohammad JI, Chigrupati S, Othman AS, Iqbal MZ. Diabetes nephropathy an obvious complication in long term Type 1 diabetes mellitus: A case study. Asian J Pharm Clin Res 2017;10:4-7.

Haghighatpanah GT, Jha A, Mallayasamy S. Study on prescribing pattern of anti-diabetic drugs among Type 2 diabetes patients with complication in South Indian teaching hospital. Asian J Pharm Clin Res 2016;9 Suppl 1:194-7.

Mosser DM, Zhang X. Interleukin-10: New perspectives on an old cytokine. Immunol Rev 2008;226:205-18.

Skommer J, Wlodkowic D, Deptala A. Larger than life: Mitochondria and the bcl-2 family. Leuk Res 2007;31:277-86.

Verzola D, Bertolotto MB, Villaggio B, Ottonello L, Dallegri F, Frumento G, et al. Taurine prevents apoptosis induced by high ambient glucose in human tubule renal cells. J Investig Med 2002;50:443-51.

Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death.N Engl J Med 2009;361:1570-83.

Cho MH. Renal fibrosis. Korean J Pediatr 2010;53:735-40.

Kozomara A, Griffiths-Jones S. MiRBase: Integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011;39:D152-7.

Samuel VT, Shulman GI. Mechanisms for insulin resistance: Common threads and missing links. Cell 2012;148:852-71.

Kriegel AJ, Liu Y, Fang Y, Ding X, Liang M. The miR-29 family: Genomics, cell biology, and relevance to renal and cardiovascular injury. Physiol Genomics 2012;44:237-44.

Ślusarz A, Pulakat L. The two faces of miR-29. J Cardiovasc Med (Hagerstown) 2015;16:480-90.

Long J, Wang Y, Wang W, Chang BH, Danesh FR. MicroRNA-29c is a signature microRNA under high glucose conditions that targets sprouty homolog 1, and its in vivo knockdown prevents progression of diabetic nephropathy. J Biol Chem 2011;286:11837-48.

Kaneto H, Katakami N, Matsuhisa M, Matsuoka TA. Role of reactive oxygen species in the progression of Type 2 diabetes and atherosclerosis. Mediators Inflamm 2010;2010:453892.

Miranda-Díaz AG, Pazarín-Villaseñor L, Yanowsky-Escatell FG, Andrade-Sierra J. Oxidative stress in diabetic nephropathy with early chronic kidney disease. J Diabetes Res 2016;2016:7047238.

Schoonmaker GC, Fallet RW, Carmines PK. Superoxide anion curbs nitric oxide modulation of afferent arteriolar ANG II responsiveness in diabetes mellitus. Am J Physiol Renal Physiol 2000;278:F302-9.

Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005;54:1615-25.

Rao C, Rao S, Prasad KH, Vidya B. Catalase and malondialdehyde levels: Possible markers for Type 2 diabetes mellitus. Euro J Biomed Pharm Sci 2017;4:232-7.

Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011;11:98-107.

Myśliwska J, Zorena K, Semetkowska-Jurkiewicz E, Rachoń D, Suchanek H, Myśliwski A, et al. High levels of circulating interleukin-10 in diabetic nephropathy patients. Eur Cytokine Netw 2005;16:117-22.

Bakheet MS. Interleukin 10 gene polymorphisms and susceptibility to nephropathy in Egyptian diabetic patients. Int J Biochem Res Rev 2017;17:1-11.

Gill PS, Wilcox CS. NADPH oxidases in the kidney. Antioxid Redox Signal 2006;8:1597-607.

Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota A. Apoptosis in glomerular sclerosis. Kidney Int 1996;49:103-11.

Pullen TJ, da Silva Xavier G, Kelsey G, Rutter GA. MiR-29a and miR-29b contribute to pancreatic beta-cell-specific silencing of monocarboxylate transporter 1 (Mct1). Mol Cell Biol 2011;31:3182-94.

Vikman J, Ma X, Hockerman GH, Rorsman P, Eliasson L. Antibody inhibition of synaptosomal protein of 25 kDa (SNAP-25) and syntaxin 1 reduces rapid exocytosis in insulin-secreting cells. J Mol Endocrinol 2006;36:503-15.

Shin ES, Sorenson CM, Sheibani N. Diabetes and retinal vascular dysfunction. J Ophthalmic Vis Res 2014;9:362-73.

Peng H, Zhong M, Zhao W, Wang C, Zhang J, Liu X, et al. Urinary miR-29 correlates with albuminuria and carotid intima-media thickness in Type 2 diabetes patients. PLoS One 2013;8:e82607.

Zhu HQ, li Q, Dong LY, Zhou Q, Wang H, Wang Y, et al. MicroRNA-29b promotes high-fat diet-stimulated endothelial permeability and apoptosis in apoE knock-out mice by down-regulating MT1 expression. Int J Cardiol 2014;176:764-70.

Mott JL, Kobayashi S, Bronk SF, Gores GJ. Mir-29 regulates mcl-1 protein expression and apoptosis. Oncogene 2007;26:6133-40.

Published

07-10-2019

How to Cite

NAWAL KHINTEEL JABBAR, ANWARA JASIB THAABAN ALMZAIEL, and FERDOUS ABASS JABER. “THE PRO-INFLAMMATORY ROLE OF MICRORNA-29b IN DIABETIC NEPHROPATHY”. Asian Journal of Pharmaceutical and Clinical Research, vol. 12, no. 10, Oct. 2019, pp. 210-3, doi:10.22159/ajpcr.2019.v12i10.34766.

Issue

Section

Original Article(s)