RING finger protein 10 is a potential drug target for diabetic vascular complications

Li,Siyu; Yu,Guiquan; Huang,Wei; Wang,Ruiyu; Pu,Peng; Chen,Ming

doi:10.3892/mmr.2019.10358

RING finger protein 10 is a potential drug target for diabetic vascular complications

Authors:
- Siyu Li
- Guiquan Yu
- Wei Huang
- Ruiyu Wang
- Peng Pu
- Ming Chen
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Affiliations: Department of Cardiology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: June 6, 2019 https://doi.org/10.3892/mmr.2019.10358
Pages: 931-938
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vascular remodeling induced by long‑term hyperglycaemia is the main pathological process in diabetic vascular complications. Thus, vascular remodeling may be a potential therapeutic target in diabetes mellitus (DM) with macrovascular disease. The present study aimed to investigate the effect of RING finger protein 10 (RNF10) on vascular remodeling under conditions of chronic hyperglycaemia stimulation. We found that overexpression of RNF10 clearly decreased intimal thickness and attenuated vascular remodeling in DM. TUNEL staining showed that apoptosis was clearly inhibited, an effect that may be mediated by decreases in Bcl‑2 protein expression. Quantitative analysis demonstrated that overexpression of RNF10 could suppress inflammation by reducing the levels of TNF‑α, and MCP‑1 mRNA and NF‑κB protein. Meanwhile, overexpression of RNF10 prevented vascular smooth muscle cell (VSMC) hyperproliferation through the downregulation of cyclin D1 and CDK4 proteins. Notably, short hairpin RNF10 (shRNF10) greatly aggravated the pathological responses of diabetic vascular remodeling. These outcomes revealed that the differential expression of RNF10 had a completely opposite effect on vascular damage under hyperglycaemia, further displaying the core function of RNF10 in regulating vascular remodeling induced by diabetes. Consequently, RNF10 could be a novel target for the treatment of diabetic vascular complications.

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1	Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U and Shaw JE: Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 103:137–149. 2014. View Article : Google Scholar : PubMed/NCBI
2	Doran AC, Meller N and McNamara CA: Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol. 28:812–819. 2008. View Article : Google Scholar : PubMed/NCBI
3	Huang CN, Chan KC, Lin WT, Su SL and Peng CH: Hibiscus sabdariffa inhibits vascular smooth muscle cell proliferation and migration induced by high glucose-a mechanism involves connective tissue growth factor signals. J Agric Food Chem. 57:3073–3079. 2009. View Article : Google Scholar : PubMed/NCBI
4	Hall JL, Matter CM, Wang X and Gibbons GH: Hyperglycemia inhibits vascular smooth muscle cell apoptosis through a protein kinase C-dependent pathway. Circ Res. 87:574–580. 2000. View Article : Google Scholar : PubMed/NCBI
5	Li H, Télémaque S, Miller RE and Marsh JD: High glucose inhibits apoptosis induced by serum deprivation in vascular smooth muscle cells via upregulation of Bcl-2 and Bcl-xl. Diabetes. 54:540–545. 2005. View Article : Google Scholar : PubMed/NCBI
6	Balasubramanyam M, Sampathkumar R and Mohan V: Is insulin signaling molecules misguided in diabetes for ubiquitin-proteasome mediated degradation? Mol Cell Biochem. 275:117–125. 2005. View Article : Google Scholar : PubMed/NCBI
7	Patterson C: Search and destroy: The role of protein quality control in maintaining cardiac function. J Mol Cell Cardio. 40:438–441. 2006. View Article : Google Scholar
8	Drews O and Taegtmeyer H: Targeting the ubiquitin-proteasome system in heart disease: The basis for new therapeutic strategies. Antioxid Redox Signal. 21:2322–2343. 2014. View Article : Google Scholar : PubMed/NCBI
9	Meiners S, Laule M, Rother W, Guenther C, Prauka I, Muschick P, Baumann G, Kloetzel PM and Stangl K: Ubiquitin-proteasome pathway as a new target for the prevention of restenosis. Circulation. 105:483–489. 2002. View Article : Google Scholar : PubMed/NCBI
10	Herrmann J, Ciechanover A, Lerman LO and Lerman A: The ubiquitin-proteasome system in cardiovascular diseases-a hypothesis extended. Cardiovasc Res. 61:11–21. 2004. View Article : Google Scholar : PubMed/NCBI
11	Seki N, Hattori A, Sugano S, Muramatsu M and Saito T: cDNA cloning, expression profile, and genomic structure of human and mouse RNF10/Rnf 10 genes, encoding a novel RING finger protein. J Hum Genet. 45:38–42. 2000. View Article : Google Scholar : PubMed/NCBI
12	Saurin AJ, Borden KL, Boddy MN and Freemont PS: Does this have a familiar RING? Trends Biochem Sci. 21:208–214. 1996. View Article : Google Scholar : PubMed/NCBI
13	Huang K, Nair AK, Muller YL, Piaggi P, Bian L, Del Rosario M, Knowler WC, Kobes S, Hanson RL, Bogardus C and Baier LJ: Whole exome sequencing identifies variation in CYB5A and RNF10 associated with adiposity and type 2 diabetes. Obesity (Silver Spring). 22:984–988. 2014. View Article : Google Scholar : PubMed/NCBI
14	Yu G, Chen J, Li S, Pu P, Huang W, Zhao Y, Wang R and Lei H: RING finger protein 10 prevents neointimal hyperplasia by promoting apoptosis in vitro and in vivo. Life Sci. 208:325–332. 2018. View Article : Google Scholar : PubMed/NCBI
15	Yang J, Fan Z, Yang J, Ding J, Yang C and Chen L: MicroRNA-24 attenuates neointimal hyperplasia in the diabetic rat carotid artery injury model by inhibiting Wnt4 signaling pathway. Int J Mol Sci. 17(pii): E7652016. View Article : Google Scholar : PubMed/NCBI
16	Yuan X, Zhang T, Yao F, Liao Y, Liu F, Ren Z, Han L, Diao L, Li Y, Zhou B, et al: THO complex-dependent posttranscriptional control contributes to vascular smooth muscle cell fate decision. Circ Res. 123:538–549. 2018. View Article : Google Scholar : PubMed/NCBI
17	Zhang Y, Xia G, Zhang Y, Liu J, Liu X, Li W, Lv Y, Wei S, Liu J and Quan J: Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway. Atherosclerosis. 263:74–81. 2017. View Article : Google Scholar : PubMed/NCBI
18	Yang D, Sun C, Zhang J, Lin S, Zhao L, Wang L, Lin R, Lv J and Xin S: Proliferation of vascular smooth muscle cells under inflammation is regulated by NF-κB p65/microRNA-17/RB pathway activation. Int J Mol Med. 41:43–50. 2018.PubMed/NCBI
19	Pan CH, Li PC, Chien YC, Yeh WT, Liaw CC, Sheu MJ and Wu CH: Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty-induced neointimal hyperplasia. Phytother Res. 32:312–320. 2018. View Article : Google Scholar : PubMed/NCBI
20	Lecker SH, Solomon V, Price SR, Kwon YT, Mitch WE and Goldberg AL: Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats. J Clin Invest. 104:1411–1420. 1999. View Article : Google Scholar : PubMed/NCBI
21	Lin J, Friesen MT, Bocangel P, Cheung D, Rawszer K and Wigle JT: Characterization of mesenchyme homeobox 2 (MEOX2) transcription factor binding to RING finger protein 10. Mol Cell Biochem. 275:75–84. 2005. View Article : Google Scholar : PubMed/NCBI
22	Paolisso G, Rizzo MR, Barbieri M, Manzella D, Ragno E and Maugeri D: Cardiovascular risk in type 2 diabetics and pharmacological regulation of mealtime glucose excursions. Diabetes Metab. 29:335–340. 2003. View Article : Google Scholar : PubMed/NCBI
23	Navarro-González Juan F and Mora-Fernández C: The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 19:433–442. 2008. View Article : Google Scholar : PubMed/NCBI
24	Winkler G, Salamon F, Harmos G, Salamon D, Speer G, Szekers O, Hajós P, Kovács M, Simon K and Cseh K: Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in type 2 diabetics and patients with android type obesity. Diabetes Res Clin Pract. 42:169–174. 1998. View Article : Google Scholar : PubMed/NCBI
25	Bayón Y, Alonso A, Hernández M, Nieto ML and Sánchez Crespo M: Mechanisms of cell signaling in immune-mediated inflammation. Cytokines Cell Mol Ther. 4:275–286. 1998.PubMed/NCBI
26	Brownlee M: The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 54:1615–1625. 2005. View Article : Google Scholar : PubMed/NCBI
27	Sherr CJ and Roberts JM: CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999. View Article : Google Scholar : PubMed/NCBI
28	Sylvester AM, Chen D, Krasinski K and Andrés V: Role of c-fos and E2F in the induction of cyclin A transcription and vascular smooth muscle cell proliferation. J Clin Invest. 101:940–948. 1998. View Article : Google Scholar : PubMed/NCBI
29	Lu Z and Hunter T: Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors. Cell Cycle. 9:2342–2352. 2010. View Article : Google Scholar : PubMed/NCBI
30	Korsmeyer SJ: BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 59 (Suppl 7):S1693–S1700. 1999.