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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

The Mechanism of miR-192 in Regulating High Glucose-Induced MCP-1 Expression in Rat Glomerular Mesangial Cells

Author(s): Fenqin Chen, Guozhu Wei, Yang Zhou, Xiaoyu Ma and Qiuyue Wang*

Volume 19, Issue 7, 2019

Page: [1055 - 1063] Pages: 9

DOI: 10.2174/1871530319666190301154640

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Abstract

Background: Although the pathogenetic mechanism of Diabetic Kidney Disease (DKD) has not been elucidated, an inflammatory mechanism may be a potential contributor. Monocyte chemotactic protein-1 (MCP-1) is suggested to be implicated in the development of DKD by playing a role in the infiltration of monocyte/macrophage. The aim of this study was to investigate the expression of MCP-1 under high glucose conditions, as well as the effects of microRNA-192 (miR-192) under these conditions, and to study the regulatory mechanism of MCP-1 in DKD.

Methods: Rat glomerular mesangial cells were cultured in high glucose or isotonic mannitol. The messenger RNA(mRNA) expression of miR-192, miR-200b, miR-200c, E-box-binding homeobox 1 (Zeb1), and MCP-1 was then detected by real-time PCR, and the protein expression of Zeb1 and MCP- 1 was assessed by western blotting. The rat mesangial cells were transfected with an miR-192 inhibitor, NC inhibitor , and transfected with siRNA Zeb1, siNC. The cells were then cultured in high glucose to detect the mRNA expression of miR-192, miR-200b, miR-200c, Zeb1, and MCP-1 using realtime PCR, and Zeb1 and MCP-1 protein expression were determined by western blotting.

Results: MiR-192, miR-200b, miR-200c, and MCP-1 were overexpressed, whereas Zeb1 was downregulated when cultured in high glucose (P < 0.05). After transfection with an miR-192 inhibitor, the expression of miR-192, miR-200b, miR-200c, and MCP-1 was downregulated, whereas Zeb1 was increased, and these differences were statistically significant (P < 0.05). The observed changes in the expression in the NC inhibitor transfection group were similar to that of non-transfected cell lines. Silencing the expression of Zeb1 resulted in a significant increase in the expression of miR-192, miR- 200b, miR-200c, and MCP-1 (P < 0.05). The observed changes in the SiNC transfection group were similar to those of non-transfected cell lines.

Conclusions: MiR-192 expression was upregulated to increase the expression of inflammatory factor MCP-1 by inhibiting the expression of Zeb1, which was mediated by breaking the regulatory loop of Zeb1 and miR-200b/c in rat mesangial cells cultured in high glucose.

Keywords: High glucose, rat glomerular mesangial cells, miR-192, miR-200b, miR-200c, MCP-1.

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[1]
Wu, C.; Lv, C.; Chen, F.; Ma, X.; Shao, Y.; Wang, Q. The function of miR-199a-5p/Klotho regulating TLR4/NF-κB p65/NGAL pathways in rat mesangial cells cultured with high glucose and the mechanism. Mol. Cell. Endocrinol., 2015, 417, 84-93.
[http://dx.doi.org/10.1016/j.mce.2015.09.024] [PMID: 26419931]
[2]
Chen, F.; Wei, G.; Xu, J.; Ma, X.; Wang, Q. Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome. BMC Complement. Altern. Med., 2018, 18(1), 192.
[http://dx.doi.org/10.1186/s12906-018-2257-y] [PMID: 29929501]
[3]
Hirakawa, Y.; Tanaka, T.; Nangaku, M. Mechanisms of metabolic memory and renal hypoxia as a therapeutic target in diabetic kidney disease. J. Diabetes Investig., 2017, 8(3), 261-271.
[http://dx.doi.org/10.1111/jdi.12624] [PMID: 28097824]
[4]
Wu, J.; Guan, T.J.; Zheng, S.; Grosjean, F.; Liu, W.; Xiong, H.; Gordon, R.; Vlassara, H.; Striker, G.E.; Zheng, F. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice. Lab. Invest., 2011, 91(10), 1459-1471.
[http://dx.doi.org/10.1038/labinvest.2011.93] [PMID: 21808238]
[5]
Gohda, T.; Nishizaki, Y.; Murakoshi, M.; Nojiri, S.; Yanagisawa, N.; Shibata, T.; Yamashita, M.; Tanaka, K.; Yamashita, Y.; Suzuki, Y.; Kamei, N. Clinical predictive biomarkers for normoalbuminuric diabetic kidney disease. Diabetes Res. Clin. Pract., 2018, 141, 62-68.
[http://dx.doi.org/10.1016/j.diabres.2018.04.026] [PMID: 29729375]
[6]
Chen, F.Q.; Wang, J.; Liu, X.B.; Ma, X.Y.; Zhang, X.B.; Huang, T.; Ma, D.W.; Wang, Q.Y. Levels of inflammatory cytokines in type 2 diabetes patients with different urinary albumin excretion rates and their correlation with clinical variables. J. Diabetes Res., 2013.2013138969
[http://dx.doi.org/10.1155/2013/138969] [PMID: 24350298]
[7]
Anderberg, R.J.; Meek, R.L.; Hudkins, K.L.; Cooney, S.K.; Alpers, C.E.; Leboeuf, R.C.; Tuttle, K.R. Serum amyloid A and inflammation in diabetic kidney disease and podocytes. Lab. Invest., 2015, 95(6), 697.
[http://dx.doi.org/10.1038/labinvest.2015.38] [PMID: 26012704]
[8]
Harjutsalo, V.; Groop, P.H. Epidemiology and risk factors for diabetic kidney disease. Adv. Chronic Kidney Dis., 2014, 21(3), 260-266.
[http://dx.doi.org/10.1053/j.ackd.2014.03.009] [PMID: 24780453]
[9]
Giunti, S.; Tesch, G.H.; Pinach, S.; Burt, D.J.; Cooper, M.E.; Cavallo-Perin, P.; Camussi, G.; Gruden, G. Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells. Diabetologia, 2008, 51(1), 198-207.
[http://dx.doi.org/10.1007/s00125-007-0837-3] [PMID: 17968528]
[10]
Wang, Q.Y.; Chen, F.Q. Clinical significance and different levels of urinary monocyte chemoattractant protein-1 in type 2 diabetes mellitus. Diabetes Res. Clin. Pract., 2009, 83(2), 215-219.
[http://dx.doi.org/10.1016/j.diabres.2008.09.048] [PMID: 19097668]
[11]
Tam, F.W.; Riser, B.L.; Meeran, K.; Rambow, J.; Pusey, C.D.; Frankel, A.H. Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy. Cytokine, 2009, 47(1), 37-42.
[http://dx.doi.org/10.1016/j.cyto.2009.04.001] [PMID: 19409809]
[12]
Morii, T.; Fujita, H.; Narita, T.; Koshimura, J.; Shimotomai, T.; Fujishima, H.; Yoshioka, N.; Imai, H.; Kakei, M.; Ito, S. Increased urinary excretion of monocyte chemoattractant protein-1 in proteinuric renal diseases. Ren. Fail., 2003, 25(3), 439-444.
[http://dx.doi.org/10.1081/JDI-120021156] [PMID: 12803507]
[13]
Liu, F.; Chen, H.Y.; Huang, X.R.; Chung, A.C.; Zhou, L.; Fu, P.; Szalai, A.J.; Lan, H.Y. C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes. Diabetologia, 2011, 54(10), 2713-2723.
[http://dx.doi.org/10.1007/s00125-011-2237-y] [PMID: 21744073]
[14]
Liao, D.; Liu, Y.Q.; Xiong, L.Y.; Zhang, L. Renoprotective effect of atorvastatin on STZ-diabetic rats through inhibiting inflammatory factors expression in diabetic rat. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(9), 1888-1893.
[PMID: 27212184]
[15]
El Mesallamy, H.O.; Ahmed, H.H.; Bassyouni, A.A.; Ahmed, A.S. Clinical significance of inflammatory and fibrogenic cytokines in diabetic nephropathy. Clin. Biochem., 2012, 45(9), 646-650.
[http://dx.doi.org/10.1016/j.clinbiochem.2012.02.021] [PMID: 22421318]
[16]
Li, J.; Lim, S.S.; Lee, E.S.; Gong, J.H.; Shin, D.; Kang, I.J.; Kang, Y.H. Isoangustone A suppresses mesangial fibrosis and inflammation in human renal mesangial cells. Exp. Biol. Med. (Maywood), 2011, 236(4), 435-444.
[http://dx.doi.org/10.1258/ebm.2010.010325] [PMID: 21367880]
[17]
Park, J.; Ryu, D.R.; Li, J.J.; Jung, D.S.; Kwak, S.J.; Lee, S.H.; Yoo, T.H.; Han, S.H.; Lee, J.E.; Kim, D.K.; Moon, S.J.; Kim, K.; Han, D.S.; Kang, S.W. MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells. Am. J. Physiol. Renal Physiol., 2008, 295(3), F749-F757.
[http://dx.doi.org/10.1152/ajprenal.00547.2007] [PMID: 18579703]
[18]
Jia, Y.; Guan, M.; Zheng, Z.; Zhang, Q.; Tang, C.; Xu, W.; Xiao, Z.; Wang, L.; Xue, Y. miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy. J. Diabetes Res., 2016.20167932765
[http://dx.doi.org/10.1155/2016/7932765] [PMID: 26942205]
[19]
Kato, M.; Arce, L.; Wang, M.; Putta, S.; Lanting, L.; Natarajan, R. A microRNA circuit mediates transforming growth factor-β1 autoregulation in renal glomerular mesangial cells. Kidney Int., 2011, 80(4), 358-368.
[http://dx.doi.org/10.1038/ki.2011.43] [PMID: 21389977]
[20]
Reddy, M.A.; Jin, W.; Villeneuve, L.; Wang, M.; Lanting, L.; Todorov, I.; Kato, M.; Natarajan, R. Pro-inflammatory role of microrna-200 in vascular smooth muscle cells from diabetic mice. Arterioscler. Thromb. Vasc. Biol., 2012, 32(3), 721-729.
[http://dx.doi.org/10.1161/ATVBAHA.111.241109] [PMID: 22247255]
[21]
Liu, H.; Zhang, X.P.; Yi, Z.W. Efficacy of antisense monocyte chemoattractant protein-1 (MCP-1) in a rat model of mesangial proliferative glomerulonephritis. Ren. Fail., 2013, 35(10), 1418-1428.
[http://dx.doi.org/10.3109/0886022X.2013.828309] [PMID: 23991758]
[22]
Tesch, G.H. MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am. J. Physiol. Renal Physiol., 2008, 294(4), F697-F701.
[http://dx.doi.org/10.1152/ajprenal.00016.2008] [PMID: 18272603]
[23]
Yoon, J.J.; Lee, Y.J.; Lee, S.M.; Kang, D.G.; Lee, H.S. Oryeongsan suppressed high glucose-induced mesangial fibrosis. BMC Complement. Altern. Med., 2015, 15, 30.
[http://dx.doi.org/10.1186/s12906-015-0542-6] [PMID: 25880429]
[24]
Feng, M.; Xu, C.B.; Wen, J.P.; Lin, G.F.; Lv, Q.; Huang, G.L. Effect of advanced glycosylation end products on oxidative stress and MCP-1 in human renal mesangial cells. Zhongguo Ying Yong Sheng Li Xue Za Zhi., 2014, 30(4), 306-310.
[25]
Zhao, B.; Li, H.; Liu, J.; Han, P.; Zhang, C.; Bai, H.; Yuan, X.; Wang, X.; Li, L.; Ma, H.; Jin, X.; Chu, Y. MicroRNA-23b Targets Ras GTPase-Activating Protein SH3 Domain-Binding Protein 2 to Alleviate Fibrosis and Albuminuria in Diabetic Nephropathy. J. Am. Soc. Nephrol., 2016, 27(9), 2597-2608.
[http://dx.doi.org/10.1681/ASN.2015030300] [PMID: 26839366]
[26]
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.
[http://dx.doi.org/10.1002/dmrr.2788] [PMID: 26891083]
[27]
Lim, L.P.; Glasner, M.E.; Yekta, S.; Burge, C.B.; Bartel, D.P. Vertebrate microRNA genes. Science, 2003, 299(5612), 1540.
[http://dx.doi.org/10.1126/science.1080372] [PMID: 12624257]
[28]
Ma, X.; Lu, C.; Lv, C.; Wu, C.; Wang, Q. The Expression of miR-192 and Its Significance in Diabetic Nephropathy Patients with Different Urine Albumin Creatinine Ratio. J. Diabetes Res., 2016.20166789402
[http://dx.doi.org/10.1155/2016/6789402] [PMID: 26881255]
[29]
Putta, S.; Lanting, L.; Sun, G.; Lawson, G.; Kato, M.; Natarajan, R. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J. Am. Soc. Nephrol., 2012, 23(3), 458-469.
[http://dx.doi.org/10.1681/ASN.2011050485] [PMID: 22223877]
[30]
Wang, G.; Kwan, B.C.; Lai, F.M.; Choi, P.C.; Chow, K.M.; Li, P.K.; Szeto, C.C. Intrarenal expression of miRNAs in patients with hypertensive nephrosclerosis. Am. J. Hypertens., 2010, 23(1), 78-84.
[http://dx.doi.org/10.1038/ajh.2009.208] [PMID: 19910931]
[31]
Wang, G.; Kwan, B.C.; Lai, F.M.; Choi, P.C.; Chow, K.M.; Li, P.K.; Szeto, C.C. Intrarenal expression of microRNAs in patients with IgA nephropathy. Lab. Invest., 2010, 90(1), 98-103.
[http://dx.doi.org/10.1038/labinvest.2009.118] [PMID: 19901913]
[32]
Wang, B.; Koh, P.; Winbanks, C.; Coughlan, M.T.; McClelland, A.; Watson, A.; Jandeleit-Dahm, K.; Burns, W.C.; Thomas, M.C.; Cooper, M.E.; Kantharidis, P. miR-200a Prevents renal fibrogenesis through repression of TGF-β2 expression. Diabetes, 2011, 60(1), 280-287.
[http://dx.doi.org/10.2337/db10-0892] [PMID: 20952520]
[33]
Srivastava, S.P.; Koya, D.; Kanasaki, K. MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT. BioMed Res. Int., 2013.2013125469
[http://dx.doi.org/10.1155/2013/125469] [PMID: 24089659]

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