Downregulation of microRNA‐592 protects mice from hypoplastic heart and congenital heart disease by inhibition of the Notch signaling pathway through upregulating KCTD10

Autor: Xue Lin, Jian-Jun Du, Ding-Yin Zeng, Xue-Feng Pang
Rok vydání: 2018
Předmět:
Heart Defects
Congenital
Male
0301 basic medicine
Small interfering RNA
Heart disease
Physiology
Clinical Biochemistry
Notch signaling pathway
Down-Regulation
Apoptosis
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
microRNA
Basic Helix-Loop-Helix Transcription Factors
medicine
Animals
cardiovascular diseases
3' Untranslated Regions
Cells
Cultured
Cell Proliferation
Binding Sites
Receptors
Notch
Heart development
Cell growth
business.industry
Myocardium
Gene Expression Regulation
Developmental
Cell Biology
medicine.disease
Repressor Proteins
Disease Models
Animal
MicroRNAs
030104 developmental biology
Potassium Channels
Voltage-Gated
030220 oncology & carcinogenesis
Cancer research
Transcription Factor HES-1
Female
business
Jagged-1 Protein
Signal Transduction
Zdroj: Journal of Cellular Physiology. 234:6033-6041
ISSN: 1097-4652
0021-9541
Popis: Evidence has demonstrated that the microRNA (miR) may play a significant role in the development of congenital heart disease (CHD). Here, we explore the mechanism of microRNA-592 (miR-592) in heart development and CHD with the involvement of KCTD10 and Notch signaling pathway in a CHD mouse model. Cardiac tissues were extracted from CHD and normal mice. Immunohistochemistry staining was performed to detect positive expression rate of KCTD10. A series of inhibitor, activators, and siRNAs was introduced to verified regulatory functions for miR-592 governing KCTD10 in CHD. Furthermore, the effect of miR-592 on cell proliferation and apoptosis was also investigated. Downregulated positive rate of KCTD10 was observed in CHD mice. Downregulation of miR-592 would upregulate expression of KCTD10 and inhibit the activation of Notch signaling pathway, thus promote cell proliferation. This study demonstrates that downregulation of miR-592 prevents CHD and hypoplastic heart by inhibition of the Notch signaling pathway via negatively binding to KCTD10.
Databáze: OpenAIRE
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