Prostacyclin IP receptor up-regulates the early expression of C/EBPβ and C/EBPδ in preadipose cells

Abstract Prostacyclin (PGI 2 ) and its stable analogue carbacyclin (cPGI 2 ) are known to trigger the protein kinase A pathway after binding to the cell surface IP receptor and to promote or enhance terminal differentiation of adipose precursor cells to adipose cells. The early expression of C/EBPβ and C/EBPδ is known to be critical for adipocyte differentiation in vitro as well as in vivo. We report herein that in Ob1771 and 3T3-F442A preadipose cells, activation of the IP receptor by specific agonists (PGI 2 , cPGI 2 and BMY 45778) is sufficient to up-regulate rapidly the expression of C/EBPβ and C/EBPδ. Cyclic AMP-elevating agents are able to substitute for IP receptor agonists, in agreement with the coupling of IP receptor to adenylate cyclase. Consistent with the fact that PGI 2 is released from preadipose cells and behaves as a paracrine/autocrine effector of adipose cell differentiation, the present results favor a key role of prostacyclin by means of the IP receptor and its intracellular signaling pathway in eliciting the critical early expression of both transcription factors.