What is the clinical evidence from this study?

Study design: Other. Population: Pulmonary fibrosis. Intervention: C-type natriuretic peptide (CNP) and long-acting CNP (LA-CNP) vs. Control littermates / untreated. Primary outcome: Pulmonary plasma leakage, immune cell infiltration, collagen deposition, and lung function decline.

What question did this study set out to answer?

This research aims to understand how C-type natriuretic peptide (CNP) influences lung fibrosis and inflammation in fibroblasts.

June 19, 2026Open Access

C-type natriuretic peptide-mediated crosstalk of endothelial cells with fibroblasts: a protective role in lung inflammation and fibrosis?

Key Result

Exogenous C-type natriuretic peptide prevented profibrotic effects in human IPF fibroblasts, and long-acting CNP reduced inflammation, collagen deposition, and lung function decline in mice.

Key Points

This research aims to understand how C-type natriuretic peptide (CNP) influences lung fibrosis and inflammation in fibroblasts.
Infusion of synthetic CNP in lung fibroblasts from patients with IPF
Generation of mouse model with conditional GC-B deletion in fibroblasts
In vivo assessment of LA-CNP effects on bleomycin-induced lung inflammation.
Exogenous CNP inhibited profibrotic effects of TGF-β and PDGF-BB in fibroblasts from both healthy and IPF patients
Fibroblast GC-B knockout mice showed increased pulmonary plasma leakage and immune cell infiltration after bleomycin
LA-CNP pretreatment significantly reduced collagen deposition and lung function decline in treated mice.

Structured PICO

Does C-type natriuretic peptide (CNP) or long-acting CNP (LA-CNP) reduce profibrotic effects and lung inflammation/fibrosis in lung fibroblasts and bleomycin-induced mouse models?

Population

Cultured lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and healthy lung specimens; genetic mouse model with conditional, fibroblast-restricted GC-B deletion; bleomycin-induced inflammatory pulmonary fibrosis mice.

Intervention

Exogenous synthetic C-type natriuretic peptide (CNP) in vitro; long-acting CNP (LA-CNP) via single subcutaneous injection in vivo.

Comparator

Control littermates (for genetic model); untreated/vehicle controls.

Outcome

Profibrotic and pro-proliferative effects in vitro; pulmonary plasma leakage, immune cell infiltration, collagen deposition, and lung function decline in vivo.surrogate

C-type natriuretic peptide and its long-acting form exert protective antifibrotic and anti-inflammatory effects in preclinical models of pulmonary fibrosis.

Abstract

Pulmonary fibrosis (PF) is a progressive, restrictive lung disease driven by fibroblast hyperactivation and increased interstitial collagen deposition. PF can be idiopathic (IPF) or secondary to severe inflammation. For instance, after severe acute coronavirus 2 (SARS-CoV-2) pneumonia, more than a third of patients develop fibrotic abnormalities. Hence there is a tremendous need for a better understanding of the molecular pathways preventing IPF, to find novel tractable targets. Infusion of exogenous synthetic C-type natriuretic peptide (CNP), activating its guanylyl cyclase B (GC-B) receptor in fibroblasts, exerted antifibrotic effects in experimental PF. To elucidate the possible therapeutical relevance, here we studied CNP actions in cultured lung fibroblasts from patients with IPF. Additionally, to dissect possible protective paracrine roles of the endogenous hormone, we generated a novel genetic mouse model with conditional, fibroblast-restricted GC-B deletion for studies of bleomycin-induced inflammatory PF. Last we investigated the potential of a long acting (LA) CNP (LA-CNP) to counteract fibrosis. In vitro exogenous CNP, via GC-B/cyclic GMP signaling, prevented the profibrotic and pro-proliferative effects of growth factors such as transforming growth factor beta (TGF-β) and platelet derived growth factor BB (PDGF-BB) on fibroblasts cultured from human “healthy” lung specimens. Notably, such inhibitory actions of CNP were fully preserved in fibroblasts from IPF patients. In vivo one week after bleomycin instillation, the fibroblast GC-B knockdown mice displayed significant increases in pulmonary plasma leakage and immune cell infiltration as well as augmented albumin and Mac-2 levels in their bronchoalveolar lavage fluid (BALF) in comparison to control littermates, indicating aggravated inflammation. Nevertheless, the extent of subsequent interstitial fibrosis and the decline of lung compliance were not different between the two genotypes. In contrast pretreatment with a single subcutaneous injection of LA-CNP exerted protective effects in bleomycin treated mice, reducing pulmonary plasma leakage, immune cell infiltration, collagen deposition and lung function decline. Together these results indicate that attenuation of CNP/GC-B signaling in fibroblasts participates in the development of inflammatory lung fibrosis and rescuing this pathway has protective effects. This work provides important insights into the potential of CNP, which in form of LA-CNP may add to the therapeutic options, improving the quality of life of patients with lung fibrosis.