Circulating miR-143-3p inhibition protects against insulin resistance in Metabolic Syndrome via targeting of the insulin-like growth factor 2 receptor

Autor: Gui Weiwei, Lin Xihua, Erik Matro, Tao Tingting, Tang Shengjie, Zhou Jiaqiang, Zheng Fenping, Li Hong, Wu Fang, Li Lin
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Down-Regulation
Receptor
IGF Type 2
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
3T3-L1 Cells
Physiology (medical)
Internal medicine
microRNA
medicine
Animals
Humans
Insulin
Gene Silencing
Obesity
RNA Processing
Post-Transcriptional
Receptor
Aged
Metabolic Syndrome
Gene knockdown
business.industry
Microarray analysis techniques
Biochemistry (medical)
Insulin-like growth factor 2 receptor
Public Health
Environmental and Occupational Health
General Medicine
Middle Aged
medicine.disease
Mice
Inbred C57BL
MicroRNAs
Cross-Sectional Studies
HEK293 Cells
030104 developmental biology
Endocrinology
Case-Control Studies
030220 oncology & carcinogenesis
Female
Insulin Resistance
Metabolic syndrome
business
Dyslipidemia
Signal Transduction
Zdroj: Translational Research. 205:33-43
ISSN: 1931-5244
DOI: 10.1016/j.trsl.2018.09.006
Popis: Metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including obesity, dyslipidemia, hyperglycemia, and hypertension. Here, we report that 27 microRNAs were found to be expressed differently in serum and urine samples of MetS patients compared to control subjects on microarray analysis. Further qualitative real time- polymerase chain reaction analyses confirmed that circulating levels of miR-143-3p were significantly elevated in MetS patients compared with controls, both in serum and urine samples. After accounting for confounding factors, high levels of miR-143-3p remained an independent risk factor for insulin resistance. Inhibition of miR-143-3p expression in mice protected against development of obesity-associated insulin resistance. Furthermore, we demonstrated that insulin-like growth factor 2 receptor (IGF2R) was among the target genes of miR-143-3p by searching 3 widely used bioinformatics databases and preliminary validation. Our experiments suggest that knockdown of circulating miR-143-3p may protect against insulin resistance in the setting of MetS via targeting of IGF2R and activation of the insulin signaling pathway. Our results characterize the miR-143-3p-IGF2R pathway as a potential target for the treatment of obesity-associated insulin resistance.
Databáze: OpenAIRE
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