{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:30:36Z","timestamp":1787621436284,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Branching morphogenesis is a key process for constructing the tree\u2010like architecture of multiple organs. The mechanisms regulating pancreatic ductal morphogenesis are still poorly understood, especially in the context of the particular pH dynamics of this organ. Indeed, ductal cells periodically release an alkaline juice to balance stomach acidity during digestion. This leads to a drop in extracellular pH (pHe) in the extracellular matrix (ECM) to maintain intracellular pH (pHi) homeostasis. Among the transporters involved in pH regulation, NHE1 also regulates epithelial branching morphogenesis in various tissues\/organs. However, neither the effect of the changing pHe nor the role of NHE1 in branching morphogenesis has been investigated in a physiomimetic model in the human pancreas. Here, using 3D organotypic cultures of human pancreatic ductal cells (HPDE), we found that cells seeded on a Matrigel rich\u2010ECM resembling normal ECM formed branched duct\u2010like structures, which did not form on a more fibrotic Collagen I\u2010rich ECM. Further, these cells overexpressed NHE1 mainly at the basolateral membrane. Ductal morphogenesis was affected by acidic pHe (pHe 6.7), which determined a hyper\u2010branched network, and this was further increased by the inhibition of NHE1. We conclude that ECM composition and extracellular acidosis modulate branching morphogenesis in pancreatic ductal HPDE cells via NHE1 activity.<\/jats:p>","DOI":"10.1002\/jcp.70156","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:02:04Z","timestamp":1772985724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Extracellular pH and NHE1 Regulate Ductal Branching Morphogenesis in Organotypic Cultures of Human Pancreatic Duct Epithelial Cells"],"prefix":"10.1002","volume":"241","author":[{"given":"Daria Di","family":"Molfetta","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Ardone","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fracasso","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Raffaella","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Tamma","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Centrone","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5025-551X","authenticated-orcid":false,"given":"Maria","family":"Barile","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tolomeo","sequence":"additional","affiliation":[{"name":"CNR Institute of Biomembranes Bioenergetics and Molecular Biotechnology Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Nisco","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan Joel","family":"Reshkin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-9135","authenticated-orcid":false,"given":"Rosa Angela","family":"Cardone","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"issue":"2","key":"e_1_2_9_2_1","first-page":"137","article-title":"Chronic Regulation of the Na\/H Antiporter","volume":"122","author":"Alpern R. 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