Prokineticin receptor-1-dependent paracrine and autocrine pathways control cardiac tcf21 fibroblast progenitor cell transformation into adipocytes and vascular cells.
Fiche publication
Date publication
octobre 2017
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr NEBIGIL-DESAUBRY Canan
Tous les auteurs :
Qureshi R, Kindo M, Arora H, Boulberdaa M, Steenman M, Nebigil CG
Lien Pubmed
Résumé
Cardiac fat tissue volume and vascular dysfunction are strongly associated, accounting for overall body mass. Despite its pathophysiological significance, the origin and autocrine/paracrine pathways that regulate cardiac fat tissue and vascular network formation are unclear. We hypothesize that adipocytes and vasculogenic cells in adult mice hearts may share a common cardiac cells that could transform into adipocytes or vascular lineages, depending on the paracrine and autocrine stimuli. In this study utilizing transgenic mice overexpressing prokineticin receptor (PKR1) in cardiomyocytes, and tcf21ERT-cre-derived cardiac fibroblast progenitor (CFP)-specific PKR1 knockout mice (PKR1 ), as well as FACS-isolated CFPs, we showed that adipogenesis and vasculogenesis share a common CFPs originating from the tcf21 epithelial lineage. We found that prokineticin-2 is a cardiomyocyte secretome that controls CFP transformation into adipocytes and vasculogenic cells in vivo and in vitro. Upon HFD exposure, PKR1 mice displayed excessive fat deposition in the atrioventricular groove, perivascular area, and pericardium, which was accompanied by an impaired vascular network and cardiac dysfunction. This study contributes to the cardio-obesity field by demonstrating that PKR1 via autocrine/paracrine pathways controls CFP-vasculogenic- and CFP-adipocyte-transformation in adult heart. Our study may open up new possibilities for the treatment of metabolic cardiac diseases and atherosclerosis.
Mots clés
Adipocytes, cytology, Adipose Tissue, metabolism, Animals, Autocrine Communication, Basic Helix-Loop-Helix Transcription Factors, metabolism, Blood Cells, cytology, Cell Lineage, Cell Transdifferentiation, Diet, High-Fat, Fibroblasts, cytology, Gene Expression Regulation, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Myocytes, Cardiac, metabolism, Neovascularization, Physiologic, PPAR gamma, genetics, Paracrine Communication, Pericardium, metabolism, Receptors, G-Protein-Coupled, metabolism, Signal Transduction, Stem Cells, metabolism
Référence
Sci Rep. 2017 10 16;7(1):12804