Molecular Pathophysioloy of fibrosis
Metabolism and Cell Signaling
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)
DESCRIPTION OF THE OFFER
Reversion of renal fibrosis by miRNA-based metabolic reprogramming
Recent work has evidenced that the progression of renal fibrosis is related to an alteration of fatty acid metabolism and more precisely to a reduction of fatty acid oxidation (FAO). Both microRNAs (miRNAs) and circadian rhythm are considered to be major regulators of lipid metabolism. We plan to develop three aims directly related to the study of the role of renal metabolism in fibrosis: 1) to decipher the contribution of microRNAs to the metabolic regulation of renal fibrogenesis 2) to study the role of the miRNAs that regulate circadian rhythm and their relationship with renal fibrosis and 3) to investigate the antifibrogenic role of miR-9-5p (previously studied in our laboratory) in renal fibrosis in relation to objectives 1 and 2. To that end we will use two genetic models in mice, one of gain-of-function (Cpt1a transgenic) and one of loss-of-function (mutant of the Clock gene, a major regulator of the circadian rhythm) and a murine model of renal fibrosis (unilateral ureteral obstruction). A key element for the identification of miRNAs involved in metabolic regulation of fibrosis will be the use of a customized miRNA array that we have designed focusing on the spotting of candidates related to fibrogenesis, redox homeostasis, FAO and mitochondrial metabolism and circadian rhythm.
Selected miRNAs will be employed as tools to promote the reversion of renal fibrosis by re-programming the metabolism of specific cellular types involved in fibrogenesis.