Prokineticin receptor-1-dependent paracrine and autocrine pathways control cardiac tcf21(+) fibroblast progenitor cell transformation into adipocytes and vascular cells

Rehana Qureshi (1) , Michel Kindo (2) , Himanshu Arora (1) , Mounia Boulberdaa (1) , Marja Steenman (3) , Canan G Nebigil (1)

1 BSC - Biotechnologie et signalisation cellulaire
2 HUS - Les Hôpitaux Universitaires de Strasbourg
3 ITX - ITX - unité de recherche de l'institut du thorax

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(TM)-derived cardiac fibroblast progenitor (CFP)-specific PKR1 knockout mice (PKR1 (tcf-/-)), 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 (tcf-/-) 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.

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie

Rehana Qureshi, Michel Kindo, Himanshu Arora, Mounia Boulberdaa, Marja Steenman, et al.. Prokineticin receptor-1-dependent paracrine and autocrine pathways control cardiac tcf21(+) fibroblast progenitor cell transformation into adipocytes and vascular cells. Scientific Reports, 2017, 7 (1), pp.12804. ⟨10.1038/s41598-017-13198-2⟩. ⟨hal-01832938⟩