open access
Vol 69, No 3 (2018)
Original paper
Submitted: 2017-10-01
Accepted: 2017-12-13
Published online: 2018-04-17
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MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy — real world evidence
1, 12, 2, 2, 2, 2
Affiliations- Shandong University, Jinan, China
- Anhui Provincial Hospital
open access
Vol 69, No 3 (2018)
Original Paper
Submitted: 2017-10-01
Accepted: 2017-12-13
Published online: 2018-04-17
Abstract
Introduction：To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms.
Methods: 202 uncontrolled type 2 diabetics, who were previously prescribed sulfonylurea monotherapy(n=100) or sulfonylurea in combination with metformin (n=102) were enrolled in the study. The amount of macrophage migration inhibitory factor(MIF) and CD74 in serum, urinary MIF to creatine ratio(UMCR), urinary CD74 to creatine ratio(UCCR), urinary albumin to creatine ratio(UACR) and urinary podocalyxin to creatine ratio (UPCR) were determined.
Results: Metabolic parameters including fasting blood glucose, postprandial 2 hours blood glucose, hemoglobin A1c, MIF and CD74 in serum were comparable between the two groups. Moreover, metformin add-on therapy showed significantly better efficacy in reducing UMCR, UCCR, UPCR and UACR in comparison with those in sulfonylurea monotherapy group, respectively. UPCR had positive correlation with UACR, UMCR and UCCR (r＝0.73, r=0.69, r=0.62, P < 0.01), respectively.
Conclusions: Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response. < p > < /p >
Abstract
Introduction：To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms.
Methods: 202 uncontrolled type 2 diabetics, who were previously prescribed sulfonylurea monotherapy(n=100) or sulfonylurea in combination with metformin (n=102) were enrolled in the study. The amount of macrophage migration inhibitory factor(MIF) and CD74 in serum, urinary MIF to creatine ratio(UMCR), urinary CD74 to creatine ratio(UCCR), urinary albumin to creatine ratio(UACR) and urinary podocalyxin to creatine ratio (UPCR) were determined.
Results: Metabolic parameters including fasting blood glucose, postprandial 2 hours blood glucose, hemoglobin A1c, MIF and CD74 in serum were comparable between the two groups. Moreover, metformin add-on therapy showed significantly better efficacy in reducing UMCR, UCCR, UPCR and UACR in comparison with those in sulfonylurea monotherapy group, respectively. UPCR had positive correlation with UACR, UMCR and UCCR (r＝0.73, r=0.69, r=0.62, P < 0.01), respectively.
Conclusions: Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response. < p > < /p >
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Keywords
metformin, type 2 diabetes, macrophage migration inhibitory factor, CD74, podocyte
About this articleTitle
MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy — real world evidence
Journal
Issue
Article type
Original paper
Pages
264-268
Published online
2018-04-17
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2782
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1341
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2018;69(3):264-268.
Keywords
metformin
type 2 diabetes
macrophage migration inhibitory factor
CD74
podocyte
Authors
Yan Xing
Shandong Ye
Yan Chen
Aihong Fan
Zhuohua Xu
Wen Jiang
References (27)- Cui S, Zhu Y, Du J, et al. CXCL8 Antagonist Improves Diabetic Nephropathy in Male Mice With Diabetes and Attenuates High Glucose-Induced Mesangial Injury. Endocrinology. 2017; 158(6): 1671–1684.
- Li S, Liu X, Lei J, et al. Crocin Protects Podocytes Against Oxidative Stress and Inflammation Induced by High Glucose Through Inhibition of NF-κB. Cell Physiol Biochem. 2017; 42(4): 1481–1492.
- Fiseha T, Tamir Z. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy. Int J Nephrol. 2016; 2016: 4647685.
- Ye H, Bai X, Gao H, et al. Urinary podocalyxin positive-element occurs in the early stage of diabetic nephropathy and is correlated with a clinical diagnosis of diabetic nephropathy. J Diabetes Complications. 2014; 28(1): 96–100.
- Petrica L, Vlad A, Gluhovschi G, et al. Proximal tubule dysfunction is associated with podocyte damage biomarkers nephrin and vascular endothelial growth factor in type 2 diabetes mellitus patients: a cross-sectional study. PLoS One. 2014; 9(11): e112538.
- Pereira SV, Dos Santos M, Rodrigues PG, et al. Increased urine podocyte-associated messenger RNAs in severe obesity are evidence of podocyte injury. Obesity (Silver Spring). 2015; 23(8): 1643–1649.
- Dandona P, Aljada A, Ghanim H, et al. Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. J Clin Endocrinol Metab. 2004; 89(10): 5043–5047.
- Chen SJ, Liao DL, Shen TW, et al. Genetic signatures of heroin addiction. Medicine (Baltimore). 2016; 95(31): e4473.
- Sanchez-Niño MD, Sanz AB, Ihalmo P, et al. The MIF receptor CD74 in diabetic podocyte injury. J Am Soc Nephrol. 2009; 20(2): 353–362.
- Hara S, Kobayashi N, Sakamoto K, et al. Podocyte injury-driven lipid peroxidation accelerates the infiltration of glomerular foam cells in focal segmental glomerulosclerosis. Am J Pathol. 2015; 185(8): 2118–2131.
- Viollet B, Guigas B, Sanz Garcia N, et al. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012; 122(6): 253–270.
- Fiorina P, Vergani A, Bassi R, et al. Role of podocyte B7-1 in diabetic nephropathy. J Am Soc Nephrol. 2014; 25(7): 1415–1429.
- Pavenstädt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003; 83(1): 253–307.
- Skoberne A, Konieczny A, Schiffer M. Glomerular epithelial cells in the urine: what has to be done to make them worthwhile? Am J Physiol Renal Physiol. 2009; 296(2): F230–F241.
- Lin H, Ye S, Xu J, et al. The alpha-lipoic acid decreases urinary podocalyxin excretion in type 2 diabetics by inhibiting oxidative stress in vivo. J Diabetes Complications. 2015; 29(1): 64–67.
- Xing Y, Ye S, Hu Y, et al. Podocyte as a potential target of inflammation: role of pioglitazone hydrochloride in patients with type 2 diabetes. Endocr Pract. 2012; 18(4): 493–498.
- Hara M, Yamagata K, Tomino Y, et al. Urinary podocalyxin is an early marker for podocyte injury in patients with diabetes: establishment of a highly sensitive ELISA to detect urinary podocalyxin. Diabetologia. 2012; 55(11): 2913–2919.
- Djudjaj S, Lue H, Rong S, et al. Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74. J Am Soc Nephrol. 2016; 27(6): 1650–1664.
- Morand EF, Leech M, Bernhagen J. MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis. Nat Rev Drug Discov. 2006; 5(5): 399–410.
- Sanchez-Niño MD, Sanz AB, Ruiz-Andres O, et al. MIF, CD74 and other partners in kidney disease: tales of a promiscuous couple. Cytokine Growth Factor Rev. 2013; 24(1): 23–40.
- Nathan DM, Buse JB, Davidson MB, et al. Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2008; 32(1): 193–203.
- Piwkowska A, Rogacka D, Jankowski M, et al. Metformin reduces NAD(P)H oxidase activity in mouse cultured podocytes through purinergic dependent mechanism by increasing extracellular ATP concentration. Acta Biochim Pol. 2013; 60(4): 607–612.
- Ravindran S, Kuruvilla V, Wilbur K, et al. Nephroprotective Effects of Metformin in Diabetic Nephropathy. J Cell Physiol. 2017; 232(4): 731–742.
- Li Cj, Lv L, Li H, et al. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid. Cardiovasc Diabetol. 2012; 11: 73.
- Zhai L, Gu J, Yang Di, et al. Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats. J Diabetes Res. 2015; 2015: 231825.
- David JR. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A. 1966; 56(1): 72–77.
- Yao XM, Ye SD, Xiao CC, et al. Metformin alleviates high glucose-mediated oxidative stress in rat glomerular mesangial cells by modulation of p38 mitogen-activated protein kinase expression in vitro. Mol Med Rep. 2015; 12(1): 520–526.
