miR-145 is differentially regulated by TGF-ss 1 and ischaemia and targets Disabled-2 expression and wnt/ss-catenin activity

Title

miR-145 is differentially regulated by TGF-ss 1 and ischaemia and targets Disabled-2 expression and wnt/ss-catenin activity

Creator

Mayorga M E; Penn M S

Publisher

Journal of Cellular and Molecular Medicine

Date

2012
2012-05

Description

The effect of wnt/beta-catenin signalling in the response to acute myocardial infarction (AMI) remains controversial. The membrane receptor adaptor protein Disabled-2 (Dab2) is a tumour suppressor protein and has a critical role in stem cell specification. We recently demonstrated that down-regulation of Dab2 regulates cardiac protein expression and wnt/beta-catenin activity in mesenchymal stem cells (MSC) in response to transforming growth factor-beta 1 (TGF-beta 1). Although Dab2 expression has been shown to have effects in stem cells and tumour suppression, the molecular mechanisms regulating this expression are still undefined. We identified putative binding sites for miR-145 in the 3'-UTR of Dab2. In MSC in culture, we observed that TGF-beta 1 treatment led to rapid and sustained up-regulation of primiR-145. Through gain and loss of function studies we demonstrate that miR-145 up-regulation was required for the down-regulation of Dab2 and increased beta-catenin activity in response to TGF-beta 1. To begin to define how Dab2 might regulate wnt/beta-catenin in the heart following AMI, we quantified myocardial Dab2 as a function of time after left anterior descending ligation. There was no significant Dab2 expression in sham-operated myocardium. Following AMI, Dab2 levels were rapidly up-regulated in cardiac myocytes in the infarct border zone. The increase in cardiac myocyte Dab2 expression correlated with the rapid and sustained down-regulation of myocardial primiR-145 expression following AMI. Our data demonstrate a novel and critical role for miR-145 expression as a regulator of Dab2 expression and beta-catenin activity in response to TGF-beta 1 and hypoxia.

Subject

gene-expression; Myocardial infarction; Cell Biology; Myocardial infarction; Research & Experimental Medicine; stem-cells; binding; pathway; cytokines; growth factors; c-myc; cell-differentiation; dab2; epithelial ovarian-cancer; myosin-vi; nasopharyngeal carcinoma

Format

Journal Article or Conference Abstract Publication

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1106-1113

Issue

5

Volume

16

Citation

Mayorga M E; Penn M S, “miR-145 is differentially regulated by TGF-ss 1 and ischaemia and targets Disabled-2 expression and wnt/ss-catenin activity,” NEOMED Bibliography Database, accessed December 2, 2021, https://neomed.omeka.net/items/show/9050.

Social Bookmarking