{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:31:03Z","timestamp":1790771463657,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fibrotic lung disease afflicts millions of people; the central problem is progressive lung destruction and remodeling. We have shown that external growth factors regulate fibroblast function not only through canonical signaling pathways but also through propagation of periodic oscillations in Ca2+. In this study, we characterized the pharmacological sensitivity of the Ca2+oscillations and determined whether a blocker of those oscillations can prevent the progression of fibrosis in vivo. We found Ca2+ oscillations evoked by exogenously applied transforming growth factor \u03b2 in normal human fibroblasts were substantially reduced by 1 \u03bcM nifedipine or 1 \u03bcM verapamil (both L-type blockers), by 2.7 \u03bcM mibefradil (a mixed L-\/T-type blocker), by 40 \u03bcM NiCl2 (selective at this concentration against T-type current), by 30 mM KCl (which partially depolarizes the membrane and thereby fully inactivates T-type current but leaves L-type current intact), or by 1 mM NiCl2 (blocks both L- and T-type currents). In our in vivo study in mice, nifedipine prevented bleomycin-induced fibrotic changes (increased lung stiffness, overexpression of smooth muscle actin, increased extracellular matrix deposition, and increased soluble collagen and hydroxyproline content). Nifedipine had little or no effect on lung inflammation, suggesting its protective effect on lung fibrosis was not due to an antiinflammatory effect but rather was due to altering the profibrotic response to bleomycin. Collectively, these data show that nifedipine disrupts Ca2+ oscillations in fibroblasts and prevents the impairment of lung function in the bleomycin model of pulmonary fibrosis. Our results provide compelling proof-of-principle that interfering with Ca2+ signaling may be beneficial against pulmonary fibrosis.<\/jats:p>","DOI":"10.1165\/rcmb.2015-0009oc","type":"journal-article","created":{"date-parts":[[2015,2,9]],"date-time":"2015-02-09T16:24:19Z","timestamp":1423499059000},"page":"450-458","source":"Crossref","is-referenced-by-count":55,"title":["Disruption of Calcium Signaling in Fibroblasts and Attenuation of Bleomycin-Induced Fibrosis by Nifedipine"],"prefix":"10.1093","volume":"53","author":[{"given":"Subhendu","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Hospital, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab","family":"A. Ayaub","sequence":"additional","affiliation":[{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Hospital, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Murphy","sequence":"additional","affiliation":[{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Hospital, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Lu","sequence":"additional","affiliation":[{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Hospital, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kolb","sequence":"additional","affiliation":[{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Hospital, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjetil","family":"Ask","sequence":"additional","affiliation":[{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Hospital, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"J. 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