Orai1 calcium channel inhibition prevents progression of chronic pancreatitis

• DOI: 10.1172/jci.insight.167645
• Publication Date: 2023-05-25T16:00:58Z
• Authors: Viktória Szabó; Noémi Csákány-Papp; Marietta Görög; Tamara Madácsy; Árpád Varga; Aletta Kiss; Bálint Tél; Boldizsár Jójárt; Tim Crul; Krisztina Dudás; Mária Bagyánszki; Nikolett Bódi; Ferhan Ayaydin; Shyam Jee; László Tiszlavicz; Kenneth A. Staude...; Sudarshan Hebbar; Petra Pallagi; József Maléth
• Keywords: Orai1; Acinar cell; Ductal cells; Pathogenesis

Patients with recurrent acute pancreatitis (RAP) are at significant risk of developing early chronic (CP), which progresses into irreversible, end-stage CP severe symptoms. There is no specific therapy in RAP or that may hinder disease progression. The pathogenesis complex and involves interactions among multiple cell types, including pancreatic acinar, ductal, stellate cells (PSC). Therefore, it pivotal to identify common pathogenic pathways these could be targeted pharmacologically. Orai1-mediated store-operated Ca2+ entry (SOCE) a ubiquitous signaling mechanism, become overactivated pathological states resulting intracellular overload. In this study, we used ex vivo preclinical models demonstrate Orai1 inhibition prevents progression CP. selective inhibitor CM5480 restored the expression SOCE-associated regulatory factor acinar cells, prevented uncontrolled elevation, protected ductal functions, mitigated immune infiltration, diminished PSC activation, proliferation migration. We suggest overactivation crucial pathogenetic event CP, prevent development