Probiotic-Derived Polyphosphate Enhances the Epithelial Barrier Function and Maintains Intestinal Homeostasis through Integrin–p38 MAPK Pathway 英文参考文献.docVIP

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Probiotic-Derived Polyphosphate Enhances the Epithelial Barrier Function and Maintains Intestinal Homeostasis through Integrin–p38 MAPK Pathway 英文参考文献.doc

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Probiotic-Derived Polyphosphate Enhances the Epithelial Barrier Function and Maintains Intestinal Homeostasis through Integrin–p38 MAPK Pathway 英文参考文献

Probiotic-DerivedPolyphosphateEnhancestheEpithelial BarrierFunctionandMaintainsIntestinalHomeostasis throughIntegrin–p38MAPKPathway ShuichiSegawa1,MikihiroFujiya2*,HiroakiKonishi2,NobuhiroUeno2,NaoyukiKobayashi1 ,Tatsuro Shigyo1,YutakaKohgo2 1Frontier Laboratories of Value Creation, Sapporo Breweries Ltd., Yaizu, Japan, 2Division of Gastroenterology and Hematology/Oncology, Department of Medicine, AsahikawaMedicalUniversity,Asahikawa,Japan Abstract Probioticsexhibitbeneficialeffectsonhumanhealth,particularlyinthemaintenanceofintestinalhomeostasisinacomplex manner notwithstanding the diversity of an intestinal flora between individuals. Thus, it is highly probable that some common molecules secreted by probiotic and/or commensal bacteria contribute to the maintenance of intestinal homeostasisandprotecttheintestinalepitheliumfrominjuriousstimuli.Toaddressthisquestion,weaimedtoisolatethe cytoprotective compound from a lactobacillus strain, Lactobacillus brevis SBC8803 which possess the ability to induce cytoprotectiveheatshockproteinsinmousesmallintestine.L.breviswasincubatedinMRSbrothandthesupernatantwas passedthroughwitha0.2-mmfilter.Caco2/bbecellsweretreatedwiththeculturesupernatant,andHSP27expressionwas evaluated by Western blotting. HSP27-inducible components were separated by ammonium sulfate precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC. Finally, we identified that the HSP27-inducible fraction was polyphosphate(polyP),asimplerepeatedstructureofphosphates,whichisacommonproductoflactobacilliandother bacteriaassociatedwithintestinalmicroflorawithoutanydefinitivephysiologicalfunctions.Then,polyPwassynthesizedby poly P-synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant-induced intestinal permeability in the mouse small intestine and pharmacological inhibitors of p38 MAPK and integrins counteract its protective effect. Daily intrar