Submitted by aml95 on Mon, 23/09/2024 - 10:41
Researchers from the Constancia group led by Ionel Sandovici and Denise Fernandez-Twinn, the Ozanne group and many other colleagues at the IMS-MRL, working in collaboration with the Universities of Cambridge, Glasgow, Montreal and Vienna, have unravelled a previously unrecognized link between Insulin-like growth factor 1 (IGF1) and IGF2.
IGFs are evolutionary conserved ligands known for their regulation of cell and organismal growth and development, with equivalent peptides present in flies and worms among other species. The study, published in Cell Reports, revealed that the mouse Mir483, located within an intron of the paternally expressed IGF2 gene, is not a self-regulated microRNA, sharing regulatory elements and imprinting with its host gene. Mir483 inhibits IGF1, among other genes, and when overexpressed during intrauterine development, triggers fetal death with associated developmental defects, prominently cardiovascular. Mir483 overexpression in postnatal life causes growth restriction, reversible by IGF1 infusion, and metabolic alterations such as increased adiposity.
The antagonistic relationship between the growth-promoting IGF2 and the growth-suppressing Mir483 may offer therapeutic potential, especially in cancer and metabolic disorders.
Reference: Sandovici, Ionel et al. Overexpression of Igf2-derived Mir483 inhibits Igf1 expression and leads to developmental growth restriction and metabolic dysfunction in mice. Cell Reports, Volume 43, Issue 9, 114750.
