{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:50:20Z","timestamp":1788313820865,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T00:00:00Z","timestamp":1545609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18J11540"],"award-info":[{"award-number":["18J11540"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) leads to lethal right ventricular failure (RVF). Periostin (POSTN) mRNA expression is increased in right ventricles (RVs) of monocrotaline (MCT)-induced PAH model rats. However, the pathophysiological role of POSTN in RVF has not been clarified. We investigated the effects of POSTN on inducible nitric oxide (NO) synthase (iNOS) expression and NO production, which causes cardiac dysfunction, in right ventricular fibroblasts (RVFbs). Male Wistar rats were intraperitoneally injected with MCT (60 mg\/kg) or saline. Three weeks after injection, RVFbs were isolated from RVs of MCT- or saline-injected rats (MCT-RVFb or CONT-RVFb). In MCT-RVFb, iNOS expression and phosphorylation of extracellular signal-regulated kinase 1\/2 (ERK1\/2), c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-\u03baB) were higher than those in CONT-RVFb. Recombinant POSTN increased iNOS expression and NO production, which were prevented by a pharmacological inhibition of ERK1\/2, JNK or NF-\u03baB in RVFbs isolated from normal rats. Culture medium of POSTN-stimulated RVFbs suppressed Ca2+ inflow through l-type Ca2+ channel (LTCC) in H9c2 cardiomyoblasts. We demonstrated that POSTN enhances iNOS expression and subsequent NO production via ERK1\/2, JNK, and NF-\u03baB signaling pathways in RVFbs. POSTN might mediate RVF through the suppression of LTCC activity of cardiomyocytes by producing NO from RVFbs in PAH model rats.<\/jats:p>","DOI":"10.3390\/ijms20010062","type":"journal-article","created":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T10:37:49Z","timestamp":1545647869000},"page":"62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Periostin Mediates Right Ventricular Failure through Induction of Inducible Nitric Oxide Synthase Expression in Right Ventricular Fibroblasts from Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats"],"prefix":"10.3390","volume":"20","author":[{"given":"Keisuke","family":"Imoto","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneyoshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Yamawaki","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lan, N., Massam, B., Kulkarni, S., and Lang, C. 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