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The role of miR-128 and MDFI in cardiac hypertrophy and heart failure: Mechanistic.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Jul; Vol. 28 (14), pp. e18546. - Publication Year :
- 2024
-
Abstract
- Heart failure (HF) prognosis depends on various regulatory factors; microRNA-128 (miR-128) is identified as a regulator of cardiac fibrosis, contributing to HF. MyoD family inhibitor (MDFI), which is reported to be related with Wnt/β-catenin pathway, is supposed to be regulated by miR-128. This study investigates the interaction between miR-128 and MDFI in cardiomyocyte development and elucidates its role in heart injury. Gene expression profiling assessed miR-128's effect on MDFI expression in HF using qPCR and Western blot analysis. Luciferase assays studied the direct interaction between miR-128 and MDFI. MTT, transwell, and immunohistochemistry evaluated the effects of miR-128 and MDFI on myocardial cells in mice HF. Genescan and luciferase assays validated the interaction between miR-128 and MDFI sequences. miR-128 mimics significantly reduced MDFI expression at mRNA and protein levels with decrease rate of 55%. Overexpression of miR-128 promoted apoptosis with the increase rate 65% and attenuated cardiomyocyte proliferation, while MDFI upregulation significantly enhanced proliferation. Elevated miR-128 levels upregulated Wnt1 and β-catenin expression, whereas increased MDFI levels inhibited these expressions. Histological analysis with haematoxylin and eosin staining revealed that miR-128 absorption reduced MDFI expression, hindering cell proliferation and cardiac repair, with echocardiography showing corresponding improvements in cardiac function. Our findings suggest miR-128 interacts with MDFI, playing a crucial role in HF management by modulating the Wnt1/β-catenin pathway. Suppression of miR-128 could promote cardiomyocyte proliferation, highlighting the potential value of the miR-128/MDFI interplay in HF treatment.<br /> (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Mice
Male
Humans
Wnt Signaling Pathway genetics
Gene Expression Regulation
Mice, Inbred C57BL
beta Catenin metabolism
beta Catenin genetics
Wnt1 Protein metabolism
Wnt1 Protein genetics
MicroRNAs genetics
MicroRNAs metabolism
Heart Failure genetics
Heart Failure metabolism
Heart Failure pathology
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Apoptosis genetics
Cardiomegaly genetics
Cardiomegaly metabolism
Cardiomegaly pathology
Cell Proliferation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 28
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 39046458
- Full Text :
- https://doi.org/10.1111/jcmm.18546