C53: A novel particulate guanylyl cyclase B receptor activator that has sustained activity in vivo with anti-fibrotic actions in human cardiac and renal fibroblasts.

ABSTRACT: The native particulate guanylyl cyclase B receptor (pGC-B) activator, C-type natriuretic peptide (CNP), induces anti-remodeling actions in the heart and kidney through the generation of the second messenger 3', 5' cyclic guanosine monophosphate (cGMP). Indeed fibrotic remodeling, particularly in cardiorenal disease states, contributes to disease progression and thus, has been a key target for drug discovery and development. Although the pGC-B/cGMP system has been perceived as a promising anti-fibrotic pathway, its therapeutic potential is limited due to the rapid degradation and catabolism of CNP by neprilysin (NEP) and natriuretic peptide clearance receptor (NPRC). The goal of this study was to bioengineer and test in vitro and in vivo a novel pGC-B activator, C53. Here we established tha

SUBMITTER: Chen Y 

PROVIDER: S-EPMC6557127 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature