Regulation of IGF-mediated cardiac growth by a novel protein encoded at the MicroRNA-1-1 and -133a-2 locus

Project: Research

Investigators

  • Douglas Matthew Anderson (PI)

Description

The intrauterine and postnatal growth of the heart is controlled by a network of transcription factors and non-coding RNAs that balance the expression of genes involved in cell proliferation, morphogenesis, protein synthesis, and contractility. In response to injury or hemodynamic stress, the adult myocardium undergoes compensatory hypertrophic growth that is characterized by an increase in cardiomyocyte cell size and the activation of fetal cardiac genes. Sustained hypertrophy is a major risk factor for the development of systolic dysfunction and the progression to clinical heart disease. Identifying and characterizing novel factors that regulate cardiac growth is vital to the development of therapeutics for the treatment heart disease. The muscle-specific microRNAs 1 and 133 play important roles as negative regulators of pathological cardiac hypertrophy. We have recently discovered a novel muscle-specific protein that is encoded at the microRNA-1-1/133a-2 locus, named MORF, which functions as a negative regulator of cardiac growth in vivo. Our preliminary data suggests that MORF represses growth by modulating IGF signaling through direct binding to the IGF2 receptor. The overall goals of this project are to further characterize the in vivo functions of MORF in regulating heart growth and to define the precise mechanisms by which MORF mediates IGF signaling. We will utilize unique transgenic and knockout mouse strains recently developed in our lab and use established in vitro techniques to characterize the novel interaction between MORF and the IGF2 receptor. These studies will provide new insight into a previously unrecognized component of the regulatory networks controlling cardiac growth and may identify new therapeutic approaches to treat pathological hypertrophy.
Award amount$95,224.00
Award date01/01/2013
Program typePostdoctoral Fellowship
Award ID13POST14570050
Effective start/end date01/01/201312/31/2014
StatusFinished