{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:40:33Z","timestamp":1790415633533,"version":"4.1.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Toronto Dominion Grant in Medical Excellence Award"},{"name":"National Institute of Health"},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense (DOD)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb (BMS)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"name":"St Joseph's healthcare"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:p> We have shown that calcium (Ca<jats:sup>2+<\/jats:sup>) oscillations in human pulmonary fibroblasts (HPFs) contribute to profibrotic effects of transforming growth factor-\u03b2 (TGF-\u03b2) and that disruption of these oscillations blunts features of pulmonary fibrosis. Prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) exerts antifibrotic effects in the lung, but the mechanisms for this action are not well defined. We thus sought to explore interactions between PGE<jats:sub>2<\/jats:sub> and the profibrotic agent TGF-\u03b2 in pulmonary fibroblasts (PFs) isolated from patients with or without idiopathic pulmonary fibrosis (IPF). PGE<jats:sub>2<\/jats:sub> inhibited TGF-\u03b2-promoted [Ca<jats:sup>2+<\/jats:sup>] oscillations and prevented the activation of Akt and Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent protein kinase-II (CaMK-II) but did not prevent activation of Smad-2 or ERK. PGE<jats:sub>2<\/jats:sub> also eliminated TGF-\u03b2-stimulated expression of collagen A1, fibronectin, and \u03b1-smooth muscle actin and reduced stress fiber formation in the HPFs. RNA sequencing revealed that HPFs preferentially express EP<jats:sub>2<\/jats:sub> receptors relative to other prostanoid receptor subtypes: EP<jats:sub>2<\/jats:sub> expression is ~10-fold higher than that of EP<jats:sub>4<\/jats:sub> receptors; EP<jats:sub>1<\/jats:sub> and EP<jats:sub>3<\/jats:sub> receptors are barely detectable; and EP<jats:sub>2<\/jats:sub>-receptor expression is ~3.5-fold lower in PFs from IPF patients than in normal HPFs. The inhibitory effects of PGE<jats:sub>2<\/jats:sub> on synthetic function and stress fiber formation were blocked by selective EP<jats:sub>2<\/jats:sub> or EP<jats:sub>4<\/jats:sub> antagonists and mimicked by selective EP<jats:sub>2<\/jats:sub> or EP<jats:sub>4<\/jats:sub> agonists, the phosphodiesterase inhibitor isobutylmethylxanthine and forskolin, all of which elevate cellular cAMP concentrations. We conclude that PGE<jats:sub>2<\/jats:sub>, likely predominantly via EP<jats:sub>2<\/jats:sub> receptors, interferes with Ca<jats:sup>2+<\/jats:sup> signaling, CaMK-II activation, and Akt activation in IPF-HPFs and HPFs treated with TGF-\u03b2. Moreover, a decreased expression of EP<jats:sub>2<\/jats:sub> receptors in pulmonary fibroblasts from IPF patients may contribute to the pathophysiology of this disease. <\/jats:p>","DOI":"10.1152\/ajplung.00403.2018","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T13:23:43Z","timestamp":1550064223000},"page":"L810-L821","source":"Crossref","is-referenced-by-count":51,"title":["Prostaglandin E<sub>2<\/sub> inhibits profibrotic function of human pulmonary fibroblasts by disrupting Ca<sup>2+<\/sup> signaling"],"prefix":"10.1152","volume":"316","author":[{"given":"Subhendu","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Firestone Institute for Respiratory Health, St. Joseph's Hospital, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sheng","sequence":"additional","affiliation":[{"name":"Firestone Institute for Respiratory Health, 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