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

Autor: Peng Pu, Ruiyu Wang, Wei Huang, Guiquan Yu, Ming Chen, Siyu Li
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Vascular smooth muscle
Apoptosis
Biochemistry
Rats
Sprague-Dawley
0302 clinical medicine
Cyclin D1
RNA
Small Interfering
Chemokine CCL2
Macrovascular disease
TUNEL assay
diabetes
NF-kappa B
Articles
Carotid Arteries
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
medicine.symptom
hyperproliferation
Signal Transduction
medicine.medical_specialty
vascular remodeling
Myocytes
Smooth Muscle
Inflammation
Nerve Tissue Proteins
Diet
High-Fat
Diabetes Mellitus
Experimental
03 medical and health sciences
Downregulation and upregulation
Internal medicine
Diabetes mellitus
Genetics
medicine
Animals
Humans
Molecular Biology
business.industry
Tumor Necrosis Factor-alpha
Cyclin-Dependent Kinase 4
medicine.disease
RING finger protein 10
Rats
030104 developmental biology
Endocrinology
Gene Expression Regulation
inflammation
Hyperglycemia
Ring finger protein 10
Insulin Resistance
business
Carrier Proteins
Diabetic Angiopathies
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: 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.
Databáze: OpenAIRE
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