Project description:Liver is primary involved in the response to insulin after feeding. Hepatocytes activates a tightly controlled genetic programme where specific sets of genes are modulates in response to insulin, for activation of the anabolic pathways. We used microarrays analysis to detail the global programme of gene expression in liver upon eIF6 haploinsufficiency and identified distinct classes of down-regulated genes and up-regulated genes during this process, that globally defines reprogramming of metabolism
Project description:Aim: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aims to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling. Methods and results: We found that miR-27b-3p expression was elevated in heart of patients with cardiac hypertrophy and in transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. MiR-27b-3p-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b-3p deletion significantly downregulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a novel miR-27b-3p target gene in the heart, which was upregulated in miR-27b-3p-null mice. Conclusions: Our study has demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.
