Role of sphingosine kinase/S1P axis in ECM remodeling of cardiac cells elicited by relaxin.

摘要: The initiation and progression of heart failure is linked to adverse cardiac remodeling the extracellular matrix (ECM) during disease mainly through deregulation myocardial metalloproteinases (MMPs). Relaxin (RLX), a peptide hormone acting as physiological effector, key regulator ECM in reproductive nonreproductive tissues. Studying primary cultures mouse muscle cells rat H9c2 cardiomyoblasts, we have obtained evidence for new signaling pathway activated by RLX induce that involves bioactive sphingolipids sphingosine-1-phosphate (S1P) ceramide. In both cell populations, recombinant human increased sphingosine kinase activity S1P formation, whereas sphingomyelin ceramide content were decreased [(3)H]serine-labeled cells. According literature, promoted MMP-2 MMP-9 expression/release. Pharmacological inhibition sphingolipid metabolism silencing 1, enzyme responsible able prevent MMP expression/release elicited expression tissue inhibitor MMPs. addition, found required regulation connective growth factor, member CCN 1-3 family genes are involved proliferation differentiation. Finally, induction cardiomyoblast maturation induced was also be counteracted formation. conclusion, these findings provide novel mechanism which acts on differentiation offer interesting therapeutic options fibrosis favor regeneration.