The Microtubule-associated Protein 1S Regulates The Role Of Autophagy-mediated Apoptosis Inhibition In Crohn's Disease Through The Wnt/β-catenin Pathway

AIM:Many autophagy-related genes,to our knowledge,have been identified as Crohn’s disease(CD)polymorphic sites by genomic wide studies.As a novel member of the microtubule-associated protein 1(MAP1)family,MAP1S is a microtubule-binding proteins involved in autophagy.However,its expression and latent values in CD has not been understood.METHODS:MAP IS expression in mucosal biopsies from patients with active CD and negtive controls was determined with immunohistochemistry.We fabricated a mice model with acute colitis stimulated by 2,4,6-trinitrobenzene sulfonicacid(TNBS),and demonstrated the presence of colitis using the disease activity index,the histologic activity index and hematoxylin and eosin staining.The cellular events and potential mechanisms were implemented with small interference RNA and an inhibitor of signaling molecule(i.e.,IWP-2)in intestinal epithelial cells(IECs)detected with western blot.The co-location of MAP IS and active-caspase3 was detected with double immunofluorescence which might indicate the basis of their coefficientRESULTS:The expression of MAP1S was absolutely increased in inflamed epithelia of active CD patients and TNBS-induced colitis epithelia.At the cellular level,silencing of MAP1S by small interference RNA(siMAP1S)prominently inhibited the expression of LC3-Ⅱ and induced the accumulation of P-catenin as well as active-caspase3,which had been well known as the executor of cellular apoptosis.Meanwhile,we found the co-location of MAP1S and LC3 with double immunofluorescence which might indicate the basis of their coefficient.Cells treated with Wnt inhibitor(i.e.,IWP-2)before siMAP1S transfection showed a reversal improvement of the siMAP1S-induced cellular apoptosis.CONCLUSION:Taken together,our results suggested that MAP1S was up-regulated in CD patients and MAP1S silencing inhibited autophagy and induced cellular apoptosis through Wnt/β-catenin signaling pathway.