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.
MeSH terms
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Animals
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Apoptosis / genetics
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Carotid Arteries / metabolism
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Carotid Arteries / pathology
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Cyclin-Dependent Kinase 4 / genetics
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Cyclin-Dependent Kinase 4 / metabolism
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Diabetes Mellitus, Experimental / etiology
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Diabetes Mellitus, Experimental / genetics*
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / pathology
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Diabetic Angiopathies / etiology
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Diabetic Angiopathies / genetics*
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Diabetic Angiopathies / metabolism
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Diabetic Angiopathies / pathology
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Diet, High-Fat / adverse effects
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Gene Expression Regulation
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Humans
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Hyperglycemia / etiology
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Hyperglycemia / genetics*
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Hyperglycemia / metabolism
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Hyperglycemia / pathology
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Insulin Resistance / genetics
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Male
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Myocytes, Smooth Muscle / metabolism*
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Myocytes, Smooth Muscle / pathology
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Signal Transduction
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Carrier Proteins
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Ccl2 protein, rat
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Ccnd1 protein, rat
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Chemokine CCL2
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NF-kappa B
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Nerve Tissue Proteins
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RNA, Small Interfering
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RNF10 protein, rat
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Tumor Necrosis Factor-alpha
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Cyclin D1
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Cdk4 protein, rat
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Cyclin-Dependent Kinase 4