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
AIM:To study the effect of salvianolate on tight junctions(TJs) and zonula occludens protein 1(ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were rand...AIM:To study the effect of salvianolate on tight junctions(TJs) and zonula occludens protein 1(ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate(12 mg/kg) treatment group,medium-dose salvianolate(24 mg/kg) treatment group,and high-dose salvianolate(48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group(P < 0.01).The number of microvilli decreased and showed irregular lengths and arrangements in the untreated group.The intercellular space between epithelial cells was wider.The TJs were discontinuous,which indicated disruption in TJ morphology in the untreated group.In the treated groups,the microvilli in the intestinal epithelium were regular and the TJs were gradually integrated and distinct.The expression of ZO-1 decreased in the small intestine of the untreated cirrhotic rats.The high expression rate of ZO-1 in ileal mucosa in the untreated group was significantly lower than that in the medium-dose salvianolate group(21.43% vs 64.29%,χ 2 = 5.25,P < 0.05),high-dose salvianolate group(21.43% vs 76.92%,χ 2 = 8.315,P < 0.01) and normal group(21.43% vs 90%,χ 2 = 10.98,P < 0.01).CONCLUSION:Salvianolate improves liver histopathological changes,repairs intestinal mucosa and TJ structure,and enhances ZO-1 expression in the small intestinal mucosa in cirrhotic rats.展开更多
AIM To investigate the interaction of Zot withmicrotubule.METHODS Zot affinity column was applied topurify Zot-binding protein（s）from crudeintestinal cell lysates.After incubation at roomtemperature,the column was w...AIM To investigate the interaction of Zot withmicrotubule.METHODS Zot affinity column was applied topurify Zot-binding protein（s）from crudeintestinal cell lysates.After incubation at roomtemperature,the column was washed and theproteins bound to the Zot affinity column wereeluted by step gradient with NaCl(0.3 mol·L<sup>-1</sup>-0.5mol·L<sup>-1</sup>).The fractions were subjected to6.0%-15.0%（w/v）gradient SDS-PAGE andthen transferred to PVDF membrane for N-terminal sequencing.Purified Zot and tauprotein were blotted by using anti-Zot or anti-tauantibodies.Finally,purified Zot was tested in anin vitro tubulin binding assay.RESULTS Fractions from Zot affinity columnyielded two protein bands with a Mr of 60 kU and45kU respectively.The N-terminal sequence ofthe 60 kU band resulted identical to β-tubulin.Zot also cross-reacts with anti-tau antibodies.Inthe in vitro tubulin binding assay,Zot co-precipitate with Mt,further suggesting that Zotpossesses tubulin-binding properties.CONCLUSION Taken together,these resultssuggest that Zot regulates the permeability ofintestinal tight junctions by binding tointracellular Mt,with the subsequent activationof the intracellular signaling leading to thepermeabilization of intercellular tight junctions.展开更多
Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary sa...Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.展开更多
Objective：To determine the relationship of thick greasy tongue fur formation and permeability of vascular endothelial cells（ECs）with the protein expression of zonula occludens-1（ZO-1）.Methods：Sprague Dawley rats...Objective：To determine the relationship of thick greasy tongue fur formation and permeability of vascular endothelial cells（ECs）with the protein expression of zonula occludens-1（ZO-1）.Methods：Sprague Dawley rats were randomly divided into a model group of severe acute pancreatitis（SAP）and a sham-operated （SO）group.The SAP rats were further divided into two subgroups on the basis of tongue-coating status：a thick greasy tongue fur group（SAP-TGF）and a normal tongue fur group（SAP-NF）.Six rats were chosen randomly from every group mentioned above for an Evans blue assay 5 days after model establishment.For the histomorphology analysis,the expressions of ZO-1 protein and mRNA were studied by hematoxylin-eosin （HE）staining,transmission electron microscope,Western blot,and Q-PCR using blood and tongue tissues, which were collected from 8 rats randomly chosen from each group.Results：The papillae density of the rat tongue surface and the caryocinesis frequency of the basal layer were significantly increased in the SAP-TGF group compared with the SO group（P0.05）.Evans blue levels in the tongue tissue of the SAP-TGF group were significantly higher than that of the SO and SAP-NF groups（P0.05）.Vascular ECs were wider and obviously fissured in the SAP-TGF group under transmission electron microscope observation.The protein and mRNA expression of ZO-1 in the SAP-TGF group were lower than those in the SAP-NF（P0.05）.Conclusions： Reproductive activity enhancement of glossal epithelial cells was one of the main characteristics of thick greasy tongue fur formation.An increase in vasopermeability was closely associated with thick greasy tongue fur formation.Tight junction structural variation of vascular ECs might play an important role in the pathological and physiological process of thick greasy tongue fur formation.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 Foundation of Chinese Medicine in Zhejiang Province Science and Technology,No.Z0102B002
文摘AIM:To study the effect of salvianolate on tight junctions(TJs) and zonula occludens protein 1(ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate(12 mg/kg) treatment group,medium-dose salvianolate(24 mg/kg) treatment group,and high-dose salvianolate(48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group(P < 0.01).The number of microvilli decreased and showed irregular lengths and arrangements in the untreated group.The intercellular space between epithelial cells was wider.The TJs were discontinuous,which indicated disruption in TJ morphology in the untreated group.In the treated groups,the microvilli in the intestinal epithelium were regular and the TJs were gradually integrated and distinct.The expression of ZO-1 decreased in the small intestine of the untreated cirrhotic rats.The high expression rate of ZO-1 in ileal mucosa in the untreated group was significantly lower than that in the medium-dose salvianolate group(21.43% vs 64.29%,χ 2 = 5.25,P < 0.05),high-dose salvianolate group(21.43% vs 76.92%,χ 2 = 8.315,P < 0.01) and normal group(21.43% vs 90%,χ 2 = 10.98,P < 0.01).CONCLUSION:Salvianolate improves liver histopathological changes,repairs intestinal mucosa and TJ structure,and enhances ZO-1 expression in the small intestinal mucosa in cirrhotic rats.
文摘AIM To investigate the interaction of Zot withmicrotubule.METHODS Zot affinity column was applied topurify Zot-binding protein（s）from crudeintestinal cell lysates.After incubation at roomtemperature,the column was washed and theproteins bound to the Zot affinity column wereeluted by step gradient with NaCl(0.3 mol·L<sup>-1</sup>-0.5mol·L<sup>-1</sup>).The fractions were subjected to6.0%-15.0%（w/v）gradient SDS-PAGE andthen transferred to PVDF membrane for N-terminal sequencing.Purified Zot and tauprotein were blotted by using anti-Zot or anti-tauantibodies.Finally,purified Zot was tested in anin vitro tubulin binding assay.RESULTS Fractions from Zot affinity columnyielded two protein bands with a Mr of 60 kU and45kU respectively.The N-terminal sequence ofthe 60 kU band resulted identical to β-tubulin.Zot also cross-reacts with anti-tau antibodies.Inthe in vitro tubulin binding assay,Zot co-precipitate with Mt,further suggesting that Zotpossesses tubulin-binding properties.CONCLUSION Taken together,these resultssuggest that Zot regulates the permeability ofintestinal tight junctions by binding tointracellular Mt,with the subsequent activationof the intracellular signaling leading to thepermeabilization of intercellular tight junctions.
文摘Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.
基金Supported by a Research Grant from Beijing Administration of Traditional Chinese Medicine(No.JJ 2008-015)
文摘Objective：To determine the relationship of thick greasy tongue fur formation and permeability of vascular endothelial cells（ECs）with the protein expression of zonula occludens-1（ZO-1）.Methods：Sprague Dawley rats were randomly divided into a model group of severe acute pancreatitis（SAP）and a sham-operated （SO）group.The SAP rats were further divided into two subgroups on the basis of tongue-coating status：a thick greasy tongue fur group（SAP-TGF）and a normal tongue fur group（SAP-NF）.Six rats were chosen randomly from every group mentioned above for an Evans blue assay 5 days after model establishment.For the histomorphology analysis,the expressions of ZO-1 protein and mRNA were studied by hematoxylin-eosin （HE）staining,transmission electron microscope,Western blot,and Q-PCR using blood and tongue tissues, which were collected from 8 rats randomly chosen from each group.Results：The papillae density of the rat tongue surface and the caryocinesis frequency of the basal layer were significantly increased in the SAP-TGF group compared with the SO group（P0.05）.Evans blue levels in the tongue tissue of the SAP-TGF group were significantly higher than that of the SO and SAP-NF groups（P0.05）.Vascular ECs were wider and obviously fissured in the SAP-TGF group under transmission electron microscope observation.The protein and mRNA expression of ZO-1 in the SAP-TGF group were lower than those in the SAP-NF（P0.05）.Conclusions： Reproductive activity enhancement of glossal epithelial cells was one of the main characteristics of thick greasy tongue fur formation.An increase in vasopermeability was closely associated with thick greasy tongue fur formation.Tight junction structural variation of vascular ECs might play an important role in the pathological and physiological process of thick greasy tongue fur formation.
