Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation

Background:Acute pancreatitis(AP) is a frequent cause for hospitalization.How-ever, moleculardeterminantsthat modulateseverity of experimentalpancreatitisareonlypartiallyunderstood.Objective:To investigatethe role of secreted protein acidic and rich in cysteine(SPARC)duringcerulein‐inducedAPinmice.Methods:APwasinducedbyrepeatedceruleininjectionsinSPARCknock‐outmice(SPARC−/−)andcontrollittermates(SPARC+/+).Secretedproteinacidicandrichincysteine expressionand severity of AP were determinedby histopathologicalscoring, immunohistochemistry,and biochemicalassays. For functionalanalysis,primary murine acinar cell cultures with subsequentamylase release assays wereemployed.Proteomeprofiler assay and ELISA were conductedfrom pancreatictissuelysates,andco‐immunofluorescencewasperformed.Results:Upon cerulein induction,SPARC expressionwas robustly induced inpancreaticstellate cells (PSCs) but not in acinar cells. Genetic SPARC ablationresultedinattenuatedseverityofAPwithsignificantlyreducedlevelsofpancreaticnecrosis, apoptosis,immune cell infiltration,and reduced fibrosis upon chronicstimulation.However,the release of amylase upon cerulein stimulationin primaryacinar cell culture from SPARC+/+and SPARC−/−was indistinguishable.Notably,immunecellderivedC‐C MotifChemokineLigand2(CCL2)washighlyelevatedinSPARC+/+pancreatictissue potentiallylinking PSC derived SPARC with CCL2 in-ductioninAP.Conclusion:SPARCmediatestheseverityofAP.ThepotentiallinkbetweenSPARCandtheCCL2axiscouldopennewavenuesfortailoredtherapeuticinterventionsinAPpatientsandwarrantsfurtherinvestigations.