A growing body of evidence suggests that tight junction(TJ)proteins play a crucial role in the pathogenesis of various diseases,including gastrointestinal(GI)cancer and hepatocellular carcinoma(HCC).TJ proteins primar...A growing body of evidence suggests that tight junction(TJ)proteins play a crucial role in the pathogenesis of various diseases,including gastrointestinal(GI)cancer and hepatocellular carcinoma(HCC).TJ proteins primarily maintain the epithelial and endothelial cells intact together through integral proteins however,recent reports suggest that they also regulate gene expression necessary for cell proliferation,angiogenesis,and metastasis through adapter proteins such as zonula occludens(ZO).ZO proteins are membrane-associated cytosolic scaffolding proteins that modulate cell proliferation by interacting with several transcription factors.Reduced ZO proteins in GI cancer and HCC are correlated with tumor development and poor prognosis.Pubmed has searched for using the keyword ZO and gastric cancer,ZO and cancer,and ZO and HCC for the last ten years to date.This review summarized the role of ZO proteins in cell proliferation and their expression in GI cancer and HCC.Furthermore,therapeutic interventions targeting ZO in GI and liver cancers are reviewed.展开更多
OBJECTIVE:To investigate the efficacy and mechanism of Qifu Lizhong enema prescription(芪附理中灌肠方,QFLZ)on intervening ulcerative colitis(UC)rat model with TCM spleen and kidney Yang insufficiency syndrome METHODS:...OBJECTIVE:To investigate the efficacy and mechanism of Qifu Lizhong enema prescription(芪附理中灌肠方,QFLZ)on intervening ulcerative colitis(UC)rat model with TCM spleen and kidney Yang insufficiency syndrome METHODS:Seventy-two male Sprague-Dawley rats were randomly assigned to six groups:normal model,mesalazine,and QFLZ high,medium,and low dose groups,each with 12 rats.After 3 d of adaptation feeding,all groups except the normal group were induced using rhubarb decoction in combination with trinitrobenzene sulfonic acid(TNBS)/55%ethanol to establish a UC rat model.Following successful modeling,the normal and model groups received daily saline enema,while the Chinese medicine and Western medicine groups received daily QFLZ and Mesalazine enema for 2 weeks respectively.The disease activity index score,hematoxylin and eosin staining,immunohistochemistry,and Western blotting were used to determine the expression of claudin 1,claudin 2,zonula occludens-1protein(ZO-1),and F-actin proteins in each rat colon tissue following treatment.RESULTS:QFLZ significantly alleviated the structural disorganization in the form of epithelial glands in the intestinal mucosa of rats with UC and retarded the progression of the disease.The intestinal mucosal epithelial cells of UC rats showed decreased expression of claudin 1,ZO-1,F-actin(P<0.05),claudin 2 appeared elevated(P<0.05),which resulted in impaired TJ.Treatment with QFLZ resulted in elevated expression of claudin 1(P<0.05),ZO-1(P<0.05)and F-actin(P<0.05)and decreased expression of claudin 2(P<0.05),which allowed for repair of the intestinal mucosal TJ,which in turn served as a treatment for UC.CONCLUSIONS:The mechanism of repairing TJ function and repairing the intestinal mucosal barrier by QFLZ may be associated with up-regulation of claudin 1,ZO-1,and F-actin levels,and down-regulation of claudin 2 expression level.展开更多
基金Supported by JIPMER intramural research grant,Indian Council of Medical Research (ICMR),New Delhi,India,No. 3/1/3 J.R.F.-2016/LS/HRD
文摘A growing body of evidence suggests that tight junction(TJ)proteins play a crucial role in the pathogenesis of various diseases,including gastrointestinal(GI)cancer and hepatocellular carcinoma(HCC).TJ proteins primarily maintain the epithelial and endothelial cells intact together through integral proteins however,recent reports suggest that they also regulate gene expression necessary for cell proliferation,angiogenesis,and metastasis through adapter proteins such as zonula occludens(ZO).ZO proteins are membrane-associated cytosolic scaffolding proteins that modulate cell proliferation by interacting with several transcription factors.Reduced ZO proteins in GI cancer and HCC are correlated with tumor development and poor prognosis.Pubmed has searched for using the keyword ZO and gastric cancer,ZO and cancer,and ZO and HCC for the last ten years to date.This review summarized the role of ZO proteins in cell proliferation and their expression in GI cancer and HCC.Furthermore,therapeutic interventions targeting ZO in GI and liver cancers are reviewed.
基金Supported by National Natural Science Foundation of China:Research on the Biological Mechanism of Nourishing Fire and Nourishing Soil Building Muscle Regeneration in Repairing Intestinal Mucosal Barrier Damage in UC Based on MLCK/Rho/PKC-Crosstalk(No.81973821)。
文摘OBJECTIVE:To investigate the efficacy and mechanism of Qifu Lizhong enema prescription(芪附理中灌肠方,QFLZ)on intervening ulcerative colitis(UC)rat model with TCM spleen and kidney Yang insufficiency syndrome METHODS:Seventy-two male Sprague-Dawley rats were randomly assigned to six groups:normal model,mesalazine,and QFLZ high,medium,and low dose groups,each with 12 rats.After 3 d of adaptation feeding,all groups except the normal group were induced using rhubarb decoction in combination with trinitrobenzene sulfonic acid(TNBS)/55%ethanol to establish a UC rat model.Following successful modeling,the normal and model groups received daily saline enema,while the Chinese medicine and Western medicine groups received daily QFLZ and Mesalazine enema for 2 weeks respectively.The disease activity index score,hematoxylin and eosin staining,immunohistochemistry,and Western blotting were used to determine the expression of claudin 1,claudin 2,zonula occludens-1protein(ZO-1),and F-actin proteins in each rat colon tissue following treatment.RESULTS:QFLZ significantly alleviated the structural disorganization in the form of epithelial glands in the intestinal mucosa of rats with UC and retarded the progression of the disease.The intestinal mucosal epithelial cells of UC rats showed decreased expression of claudin 1,ZO-1,F-actin(P<0.05),claudin 2 appeared elevated(P<0.05),which resulted in impaired TJ.Treatment with QFLZ resulted in elevated expression of claudin 1(P<0.05),ZO-1(P<0.05)and F-actin(P<0.05)and decreased expression of claudin 2(P<0.05),which allowed for repair of the intestinal mucosal TJ,which in turn served as a treatment for UC.CONCLUSIONS:The mechanism of repairing TJ function and repairing the intestinal mucosal barrier by QFLZ may be associated with up-regulation of claudin 1,ZO-1,and F-actin levels,and down-regulation of claudin 2 expression level.
