Prokineticins are defined as cytokines (immunoregulatory proteins), adipokines (adipocyte-secreted hormone), angiogenic (increasing vessel formation), or aneroxic (lowering food intake) hormones. Prokineticin-mediated signaling plays a key role in the development of obesity and cardiovascular diseases. Two forms of prokineticins exist in circulation and in various tissues including the brain, heart, kidney, and adipose. Prokineticins act on the two G protein-coupled receptors, namely, PKR1 and PKR2.
We have established how prokineticin signaling through autocrine and paracrine regulations control the functions of cardiomyocytes, endothelial cells and epicardial progenitor cells (EPDCs). We also unraveled that a PKR1-driven epigenetic switch regulates EPDC stemness and fate (adipogenesis/vasculogenesis) in the context of high calorie intact. Moreover, we found that prokineticin-2/PKR1 signaling may act as a new connector between development of obesity and heart failure.
We also identified the first non-peptide PKR1 agonists and demonstrated their cardioprotective activities in a mouse model of heart failure.