Abstract P008: Fibronectin Enhances Survival and Proliferation via Pim-1 and β1 Integrin in Cardiac Progenitor Cells

Abstract

Background: Cardiac Progenitor Cells (CPC) are pivotally involved in cardiac repair. Extracellular matrix (ECM) components also contribute decisively in cardiac remodeling after myocardial infarction (MI). However, impact of ECM on CPC function and the involved signaling pathways have not been clearly elucidated. This study examines the relationship of ECM to cardioprotective signaling mediated by Pim-1, a serine/threonine kinase downstream of Akt, in CPC. Methods: Isolated mouse CPCs were plated on fibronectin (FN) or albumin coated dishes. FACS analysis and fluorescence based cell quantification have been used to determine viability and proliferation under stress and growth conditions. Signaling pathways were analyzed by immunoblotting, qRT-PCR and siRNA. Immunhistochemistry (IHC) has been used for in vivo studies after MI in mice. Results: FN inhibits starvation and staurosporine induced cell death in CPCs and promotes proliferation in conjunction with induction of Pim-1 expression. Protective and pro-proliferative effects of FN are abrogated by inhibition of Pim-1. Fibronectin signaling operates through the β1 integrin receptor that is crucial for FN-mediated signaling. Ongoing studies correlate these observations with in vivo responses to cardiomyopathic injury such as infarction challenge. Conclusion: FN provides pro-survival and pro-proliferative effects in CPCs in a Pim-1 kinase and β1 integrin dependent manner. Involved molecules colocalize in vivo in an infarction injury model. The causal contribution of FN in regeneration and wound healing after MI is to be confirmed by studies of a conditional FN knock-out mouse that is under construction.