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Erschienen in: International Journal of Diabetes in Developing Countries 1/2022

21.07.2021 | Original Article

Resistin, TNF-α, and microRNA 124-3p expressions in peripheral blood mononuclear cells are associated with diabetic nephropathy

verfasst von: Amin Monjezi, Azam Khedri, Mehrnoosh Zakerkish, Ghorban Mohammadzadeh

Erschienen in: International Journal of Diabetes in Developing Countries | Ausgabe 1/2022

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Abstract

Introduction

Diabetic nephropathy causes chronic kidney disease and renal failure globally. We investigated the mRNA expression of resistin, TNF-α, and microRNA 124-3p (miR-124-3p) in peripheral blood mononuclear cells (PBMCs) of diabetic patients with and without nephropathy.

Methods

The mRNA expression of target genes in isolated PBMCs from whole blood was determined using real-time quantitative reverse transcription (RT) polymerase chain reaction (qRT-PCR). Demographic and clinical characteristics of study patients were also measured by standard methods.

Results

Relative expression of resistin and TNF-α was significantly increased (approximately 10-fold, and 1.5-fold respectively) in patients with nephropathy compared to that in patients without nephropathy (p < 0.001). However, the miR-124-3p expression was significantly decreased (approximately 10-fold) in patients with nephropathy in comparison to that in patients without nephropathy (p < 0.05). The expression of resistin was significantly associated with inflammatory markers such as creatinine, BUN, TNF-α, and miR-124-3p. The high expression of resistin was significantly associated with diabetic nephropathy (OR = 1.145; 95% C = 1.1–18.289, p = 0.024). The diagnostic performance of resistin, TNF-α, and miR-124-3p was significant based on ROC curve analysis (0.803, 95% CI: 0.723–0.926; 0.705, %95 CI: 0.559–0.851; and 0.707, 95% CI: 0.559–0.855, respectively). Thus, they can represent a diabetic biomarker for reflecting an advanced stage of the disease and inflammatory condition.

Conclusions

Our findings indicated that high expression of resistin in PBMCs is associated with diabetic nephropathy. Additionally, we suggested that the expression of resistin, TNF-α, and miR-124-3p in PBMCs of diabetic patients may be represented as predictive biomarkers for the diagnosis of nephropathy.
Literatur
1.
Zurück zum Zitat Gheith O, Farouk N, Nampoory N, Halim MA, al-Otaibi T. Diabetic kidney disease: worldwide difference of prevalence and risk factors. J Nephropharmacol. 2016;5(1):49–56.PubMed Gheith O, Farouk N, Nampoory N, Halim MA, al-Otaibi T. Diabetic kidney disease: worldwide difference of prevalence and risk factors. J Nephropharmacol. 2016;5(1):49–56.PubMed
2.
Zurück zum Zitat Steppan CM, Bailey ST, Bhat S, Elizabeth J, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307–12.CrossRefPubMed Steppan CM, Bailey ST, Bhat S, Elizabeth J, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307–12.CrossRefPubMed
3.
Zurück zum Zitat Patel L, Buckels AC, IKinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun. 2003;300:472–6.CrossRefPubMed Patel L, Buckels AC, IKinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun. 2003;300:472–6.CrossRefPubMed
4.
Zurück zum Zitat Dietze D, Koenen M, Rohrig K, Horikoshi H, Hauner H, Eckel J. Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Diabetes. 2002;51:2369–76.CrossRefPubMed Dietze D, Koenen M, Rohrig K, Horikoshi H, Hauner H, Eckel J. Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Diabetes. 2002;51:2369–76.CrossRefPubMed
6.
Zurück zum Zitat Himmerich H, Fulda S, Linseisen J, Seiler H, Wolfram G, Himmerich S, Gedrich K, Pollmächer T. TNF-alpha, soluble TNF receptor and interleukin-6 plasma levels in the general population. Eur Cytokine Netw. 2006;17:196–201.PubMed Himmerich H, Fulda S, Linseisen J, Seiler H, Wolfram G, Himmerich S, Gedrich K, Pollmächer T. TNF-alpha, soluble TNF receptor and interleukin-6 plasma levels in the general population. Eur Cytokine Netw. 2006;17:196–201.PubMed
7.
Zurück zum Zitat Moller DE. Potential role of TNF alpha in the pathogenesis of insulin resistance and type 2 diabetes. Ternds Endocrinol Metab. 2000;11:212–7.CrossRef Moller DE. Potential role of TNF alpha in the pathogenesis of insulin resistance and type 2 diabetes. Ternds Endocrinol Metab. 2000;11:212–7.CrossRef
8.
Zurück zum Zitat Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:139239.CrossRefPubMedPubMedCentral Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:139239.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Bhatt K, Mi QS, Dong Z. MicroRNAs in kidneys: biogenesis, regulation, and pathophysiological roles. Am J Physiol Renal Physiol. 2011;300:nF602-F610.CrossRef Bhatt K, Mi QS, Dong Z. MicroRNAs in kidneys: biogenesis, regulation, and pathophysiological roles. Am J Physiol Renal Physiol. 2011;300:nF602-F610.CrossRef
10.
Zurück zum Zitat Fernandez-Valverde SL, Taft RJ, Mattick JS. MicroRNAs in β-cell biology, insulin resistance, diabetes and its complications. Diabetes. 2011;60:1825–31.CrossRefPubMedPubMedCentral Fernandez-Valverde SL, Taft RJ, Mattick JS. MicroRNAs in β-cell biology, insulin resistance, diabetes and its complications. Diabetes. 2011;60:1825–31.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Shantikumar S, Caporali A, Emanueli C. Role of microRNAs in diabetes and its cardiovascular complications. Cardiovasc Res. 2012;93(4):583–93.CrossRefPubMed Shantikumar S, Caporali A, Emanueli C. Role of microRNAs in diabetes and its cardiovascular complications. Cardiovasc Res. 2012;93(4):583–93.CrossRefPubMed
13.
14.
Zurück zum Zitat Bhatt K, Kato M, Natarajan R. Minireview: emerging roles of microRNAs in the pathophysiology of renal diseases. Am J Physiol Renal Physiol. 2016;310:F109–18.CrossRefPubMed Bhatt K, Kato M, Natarajan R. Minireview: emerging roles of microRNAs in the pathophysiology of renal diseases. Am J Physiol Renal Physiol. 2016;310:F109–18.CrossRefPubMed
15.
Zurück zum Zitat Guay C, Regazzi R. New emerging tasks for microRNAs in the control of β-cell activities. Biochimica et Biophysica Acta. 2016;1861:2121–9.CrossRefPubMed Guay C, Regazzi R. New emerging tasks for microRNAs in the control of β-cell activities. Biochimica et Biophysica Acta. 2016;1861:2121–9.CrossRefPubMed
16.
Zurück zum Zitat Sebastiani G, Po A, Miele E, et al. MicroRNA-124a is hyper expressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion. Acta Diabetologica. 2015;52:523–30.CrossRefPubMed Sebastiani G, Po A, Miele E, et al. MicroRNA-124a is hyper expressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion. Acta Diabetologica. 2015;52:523–30.CrossRefPubMed
17.
Zurück zum Zitat Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9:513–21.CrossRefPubMed Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9:513–21.CrossRefPubMed
18.
Zurück zum Zitat Yang Z, Chen H, Si H, et al. Serum miR-23a, a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes. Acta Diabetologica. 2014;51:823–31.CrossRefPubMed Yang Z, Chen H, Si H, et al. Serum miR-23a, a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes. Acta Diabetologica. 2014;51:823–31.CrossRefPubMed
19.
Zurück zum Zitat Nassirpour R, Raj D, Townsend R, Argyropoulos C. MicroRNA biomarkers in clinical renal disease: from diabetic nephropathy, renal transplantation and beyond. Food Chem Toxicol. 2016;98:73–88.CrossRefPubMed Nassirpour R, Raj D, Townsend R, Argyropoulos C. MicroRNA biomarkers in clinical renal disease: from diabetic nephropathy, renal transplantation and beyond. Food Chem Toxicol. 2016;98:73–88.CrossRefPubMed
20.
Zurück zum Zitat Li D, Lub Z, Jiaa J, Zhenga Z, Lina S. MiR-124 is related to podocytic adhesive capacity damage in STZ-induced uninephrectomized diabetic rats. Kidney Blood Press Res. 2013;37:422–31.CrossRefPubMed Li D, Lub Z, Jiaa J, Zhenga Z, Lina S. MiR-124 is related to podocytic adhesive capacity damage in STZ-induced uninephrectomized diabetic rats. Kidney Blood Press Res. 2013;37:422–31.CrossRefPubMed
21.
Zurück zum Zitat Li D, Lu Z, Jia J, Zheng Z, Lin S. Changes in microRNAs associated with podocytic adhesion damage under mechanical stress. J Renin Angiotensin Aldosterone Syst. 2013;14(2):97–102.CrossRefPubMed Li D, Lu Z, Jia J, Zheng Z, Lin S. Changes in microRNAs associated with podocytic adhesion damage under mechanical stress. J Renin Angiotensin Aldosterone Syst. 2013;14(2):97–102.CrossRefPubMed
22.
Zurück zum Zitat Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O’Rahilly S. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001;50:2199–202.CrossRefPubMed Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O’Rahilly S. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001;50:2199–202.CrossRefPubMed
23.
Zurück zum Zitat McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S. Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab. 2002;87:2407.CrossRefPubMed McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S. Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab. 2002;87:2407.CrossRefPubMed
24.
Zurück zum Zitat Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 2004;1:161–8.CrossRef Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 2004;1:161–8.CrossRef
25.
Zurück zum Zitat Anderson PD, Mehta NN, Wolfe ML, et al. Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab. 2007;92:2272–9.CrossRefPubMed Anderson PD, Mehta NN, Wolfe ML, et al. Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab. 2007;92:2272–9.CrossRefPubMed
26.
Zurück zum Zitat Peraldi P, Hotamisligil GS, Buurman WA, White MF. Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J Biol Chem. 1996;271:13018–22.CrossRefPubMed Peraldi P, Hotamisligil GS, Buurman WA, White MF. Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J Biol Chem. 1996;271:13018–22.CrossRefPubMed
27.
Zurück zum Zitat Kaser S, Kaser A, Sandhofer A, Ebenbichler CF, Tilg H, Patsch JR. Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun. 2003;309(2):286–90.CrossRefPubMed Kaser S, Kaser A, Sandhofer A, Ebenbichler CF, Tilg H, Patsch JR. Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun. 2003;309(2):286–90.CrossRefPubMed
28.
Zurück zum Zitat Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H, Anai M, Onishi Y, Ono H, Inukai K, Abe M, Fukushima Y, Kikuchi M, Oka Y, Asano T. Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells. Diabetes. 2002;51:1737–44.CrossRefPubMed Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H, Anai M, Onishi Y, Ono H, Inukai K, Abe M, Fukushima Y, Kikuchi M, Oka Y, Asano T. Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells. Diabetes. 2002;51:1737–44.CrossRefPubMed
29.
30.
Zurück zum Zitat Regmi A, Liu G, Zhong X, Hu S, Ma R, Gou L, et al. Evaluation of serum microRNAs in patients with diabetic kidney disease: a nested case-controlled study and bioinformatics analysis. Med Sci Monit. 2019;25:1699–708.CrossRefPubMedPubMedCentral Regmi A, Liu G, Zhong X, Hu S, Ma R, Gou L, et al. Evaluation of serum microRNAs in patients with diabetic kidney disease: a nested case-controlled study and bioinformatics analysis. Med Sci Monit. 2019;25:1699–708.CrossRefPubMedPubMedCentral
Metadaten
Titel
Resistin, TNF-α, and microRNA 124-3p expressions in peripheral blood mononuclear cells are associated with diabetic nephropathy
verfasst von
Amin Monjezi
Azam Khedri
Mehrnoosh Zakerkish
Ghorban Mohammadzadeh
Publikationsdatum
21.07.2021
Verlag
Springer India
Erschienen in
International Journal of Diabetes in Developing Countries / Ausgabe 1/2022
Print ISSN: 0973-3930
Elektronische ISSN: 1998-3832
DOI
https://doi.org/10.1007/s13410-021-00966-0

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