The interaction of desmin and nkx2.5 in cardiac stem cells

The transcription factor Nkx2.5 and the intermediate filament protein desmin are simultaneously expressed in cardiac progenitor cells during commitment of primitive mesoderm to the cardiomyogenic lineage and mutations in both genes are related to overlapping and very diverse pathological cardiac phenotypes. Desmin up-regulates Nkx2.5 expression in embryoid bodies, activates nkx2.5 reporter genes in heart cells, rescues nkx2.5 haploinsufficiency in cardiac progenitor cells, and is found in some nuclei of cardiac progenitor cells where it physical interacts with enhancer and promoter elements of the Nkx2.5 gene. This set of data suggests that desmin may directly contribute to cardiogenic commitment and myocardial differentiation by influencing the transcription of the nkx2.5 gene in cardiac progenitor cells. Hence we propose to unravel the molecular interactions of desmin and Nkx2.5 proteins with the Nkx2.5 and desmin genes in cardiac progenitor cells in order to contribute to a causal understanding of the role of desmin and nkx2.5 in cardiac progenitor cell homeostasis.

Desmin seems not to directly influence the expression of nkx2.5 in cardiac stem cell lines. However, desmin significantly promotes the expression of SPARC. SPARC in turn promotes cardiomyogenesis and the expression of some gene important for the development of cardiac cells and promotes their longevity. Desmin and SPARC together seem to influence MAPK signaling in a post-translational manner. Cardiac stem cells secret substantial amounts of SPARC and hence could fulfil an endocrine function in the adult and ageing heart.