{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:27:45Z","timestamp":1783700865911,"version":"3.55.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/16\/7\/32357"],"award-info":[{"award-number":["RG\/16\/7\/32357"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD), hepatic fibrosis, and portal hypertension constitute an increasing public health problem due to the growing prevalence of obesity and diabetes. C-type natriuretic peptide (CNP) is an endogenous regulator of cardiovascular homeostasis, immune cell reactivity, and fibrotic disease. Thus, we investigated a role for CNP in the pathogenesis of MASLD. Wild-type (WT), global CNP (gbCNP\u2212\/\u2212), and natriuretic peptide receptor-C (NPR-C\u2212\/\u2212) knockout mice were fed a choline-deficient defined amino acid diet or administered CCl4. Liver damage was assessed by histological and biochemical analyses, with steatosis and portal vein size determined by ultrasound. Portal vein pressure and reactivity were measured in vivo and ex vivo, respectively. Pharmacological CNP delivery was used to evaluate prospective therapeutic benefit, and plasma CNP concentration was compared in controls and patients with cirrhosis. Circulating CNP concentration was lower in patients with cirrhosis compared with controls. gbCNP\u2212\/\u2212 mice were more susceptible, versus WT, to advanced steatohepatitis and hepatic fibrosis, characterized by increased immune cell infiltration, fibrosis, ballooning, plasma alanine aminotransferase concentration, and up-regulation of markers driving these processes. gbCNP\u2212\/\u2212 mice had increased portal vein diameter and pressure, underpinned by CNP insensitivity. NPR-C\u2212\/\u2212 animals recapitulated, comparatively, the exaggerated pathogenic phenotype in gbCNP\u2212\/\u2212 mice, whereas CNP reduced hepatic stellate cell proliferation via NPR-B-dependent inhibition of extracellular signal-related kinase 1\/2. Administration of CNP reversed many aspects of disease severity. These data define a new intrinsic role for CNP in offsetting the pathogenesis of MASLD, hepatic fibrosis, and portal hypertension and the potential for targeting CNP signaling for treating these disorders.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgae579","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T17:54:51Z","timestamp":1735581291000},"source":"Crossref","is-referenced-by-count":2,"title":["Endogenous C-type natriuretic peptide offsets the pathogenesis of steatohepatitis, hepatic fibrosis, and portal hypertension"],"prefix":"10.1093","volume":"4","author":[{"given":"Cristina","family":"Perez-Ternero","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts and The London, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ ,","place":["United 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