C-type natriuretic peptide/cGMP/FoxO3 signaling attenuates hyperproliferation of pericytes from patients with pulmonary arterial hypertension

Autor: Swati Dabral, Minhee Noh, Franziska Werner, Lisa Krebes, Katharina Völker, Christopher Maier, Ivan Aleksic, Tatyana Novoyatleva, Stefan Hadzic, Ralph Theo Schermuly, Vinicio A. de Jesus Perez, Michaela Kuhn
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Communications Biology, Vol 7, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-024-06375-3
Popis: Abstract Pericyte dysfunction, with excessive migration, hyperproliferation, and differentiation into smooth muscle-like cells contributes to vascular remodeling in Pulmonary Arterial Hypertension (PAH). Augmented expression and action of growth factors trigger these pathological changes. Endogenous factors opposing such alterations are barely known. Here, we examine whether and how the endothelial hormone C-type natriuretic peptide (CNP), signaling through the cyclic guanosine monophosphate (cGMP) -producing guanylyl cyclase B (GC-B) receptor, attenuates the pericyte dysfunction observed in PAH. The results demonstrate that CNP/GC-B/cGMP signaling is preserved in lung pericytes from patients with PAH and prevents their growth factor-induced proliferation, migration, and transdifferentiation. The anti-proliferative effect of CNP is mediated by cGMP-dependent protein kinase I and inhibition of the Phosphoinositide 3-kinase (PI3K)/AKT pathway, ultimately leading to the nuclear stabilization and activation of the Forkhead Box O 3 (FoxO3) transcription factor. Augmentation of the CNP/GC-B/cGMP/FoxO3 signaling pathway might be a target for novel therapeutics in the field of PAH.
Databáze: Directory of Open Access Journals
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