Tissue Barriers最新文献

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Dual role of E-cadherin in cancer cells. e -钙粘蛋白在癌细胞中的双重作用。
IF 3.1
Tissue Barriers Pub Date : 2022-10-02 Epub Date: 2021-11-25 DOI: 10.1080/21688370.2021.2005420
Svetlana N Rubtsova, Irina Y Zhitnyak, Natalya A Gloushankova
{"title":"Dual role of E-cadherin in cancer cells.","authors":"Svetlana N Rubtsova,&nbsp;Irina Y Zhitnyak,&nbsp;Natalya A Gloushankova","doi":"10.1080/21688370.2021.2005420","DOIUrl":"https://doi.org/10.1080/21688370.2021.2005420","url":null,"abstract":"<p><p>E-cadherin is the main component of epithelial adherens junctions (AJs), which play a crucial role in the maintenance of stable cell-cell adhesion and overall tissue integrity. Down-regulation of E-cadherin expression has been found in many carcinomas, and loss of E-cadherin is generally associated with poor prognosis in patients. During the last decade, however, numerous studies have shown that E-cadherin is essential for several aspects of cancer cell biology that contribute to cancer progression, most importantly, active cell migration. In this review, we summarize the available data about the input of E-cadherin in cancer progression, focusing on the latest advances in the research of the various roles E-cadherin-based AJs play in cancer cell dissemination. The review also touches upon the \"cadherin switching\" in cancer cells where N- or P-cadherin replace or are co-expressed with E-cadherin and its influence on the migratory properties of cancer cells.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621038/pdf/KTIB_10_2005420.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Bacterial effluxome as a barrier against antimicrobial agents: structural biology aspects and drug targeting. 细菌排出体作为抗微生物药物的屏障:结构生物学方面和药物靶向。
IF 3.1
Tissue Barriers Pub Date : 2022-10-02 DOI: 10.1080/21688370.2021.2013695
Pownraj Brindangnanam, Ajit Ramesh Sawant, K Prashanth, Mohane Selvaraj Coumar
{"title":"Bacterial effluxome as a barrier against antimicrobial agents: structural biology aspects and drug targeting.","authors":"Pownraj Brindangnanam,&nbsp;Ajit Ramesh Sawant,&nbsp;K Prashanth,&nbsp;Mohane Selvaraj Coumar","doi":"10.1080/21688370.2021.2013695","DOIUrl":"https://doi.org/10.1080/21688370.2021.2013695","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is fast becoming a medical crisis affecting the entire global population. The bacterial membrane is the first layer of defense for the bacteria against antimicrobial agents (AMA), specifically transporters in the membrane efflux these AMA out of the bacteria and plays a significant role in the AMR development. Understanding the structure and the functions of these efflux transporters is essential to overcome AMR. This review discusses efflux transporters (primary, secondary, and tripartite), their domain architectures, substrate specificities, and efflux pump inhibitors (EPI). Special emphasis on nosocomial ESKAPEE (<i>Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter</i> spp. and <i>Escherichia coli</i>) pathogens, their multidrug efflux targets and inhibitors are discussed. Deep knowledge about the functioning of efflux pumps and their structural aspects will open up opportunities for developing new EPI, which could be used along with AMA as combination therapy to overcome the emerging AMR crisis.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621062/pdf/KTIB_10_2013695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10423375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Destiny of airway disease: interplay between epithelial barrier and the innate immune system. 气道疾病的命运:上皮屏障与先天免疫系统的相互作用。
IF 3.1
Tissue Barriers Pub Date : 2022-10-02 DOI: 10.1080/21688370.2021.2020706
Hasan Yüksel, Seda Tunca
{"title":"Destiny of airway disease: interplay between epithelial barrier and the innate immune system.","authors":"Hasan Yüksel,&nbsp;Seda Tunca","doi":"10.1080/21688370.2021.2020706","DOIUrl":"https://doi.org/10.1080/21688370.2021.2020706","url":null,"abstract":"<p><p>When the organism encounters a foreign substance, it responds with mutual and regular interactions at different stages of the immune system. In airway diseases, the first encounter is at the epithelial level, where innate immune cells and their responses form the first leg of the protective mechanism. The most important barrier for environmental damage is the epithelial barrier. However, the epithelial barrier is not just a mechanical barrier. The formation of the microbiome on the epithelium and the tolerance or intolerance to environmental factors are vital. This vital balance is maintained between the epithelial surface and the subepithelial innate immune system. This is achieved by the epithelial line, which is a mechanical and functional barrier between them. In this respect, epithelial barrier function preservation has an important role in the development and prognosis of airway disease.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624204/pdf/KTIB_10_2020706.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10450704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cell penetrating peptides coupled to an endothelial nitric oxide synthase sequence alter endothelial permeability. 细胞穿透肽偶联到内皮一氧化氮合酶序列改变内皮通透性。
IF 3.1
Tissue Barriers Pub Date : 2022-10-02 DOI: 10.1080/21688370.2021.2017226
Stephen R Koch, Ryan J Stark
{"title":"Cell penetrating peptides coupled to an endothelial nitric oxide synthase sequence alter endothelial permeability.","authors":"Stephen R Koch,&nbsp;Ryan J Stark","doi":"10.1080/21688370.2021.2017226","DOIUrl":"https://doi.org/10.1080/21688370.2021.2017226","url":null,"abstract":"<p><p>Delivery of cargo to cells through the use of cell-penetrating peptide (CPP) sequences is an area of rich investigation for targeted therapeutics. Specific to the endothelium, the layer of cells that cover every blood vessel in the body, the loss or alteration of a key enzyme, endothelial nitric oxide synthase (eNOS), is known to contribute to endothelial health during severe, infectious challenge. While the beneficial effects of eNOS are often thought to be mediated through the generation of nitric oxide, some protection is theorized to be through eNOS binding to regulatory pathways via a pentabasic RRKRK motif. We hypothesized that delivery of the eNOS-RRKRK peptide sequence using common CPPs would allow protection against gram-negative lipopolysaccharide (LPS). Combination of the eNOS-RRKRK sequence to the CPP antennapedia (AP) reduced the impact of LPS-induced permeability in cultured human microvascular endothelial cells (HMVECs) as measured by transendothelial electrical resistance (TEER). There was also a modest reduction in cytokine production, however it was observed that AP alone significantly impaired LPS-induced endothelial permeability and cytokine production. In comparison, the CPP trans-activator of transcription (TAT) did not significantly alter endothelial inflammation by itself. When TAT was coupled to the eNOS-RRKRK sequence, protection against LPS-induced permeability was still demonstrated, however cytokine production was not reduced. These data demonstrate that the RRKRK sequence of eNOS can offer some NO-independent protection against LPS-mediated endothelial inflammation, however the degree of protection is highly dependent on the type of CPP utilized for cargo delivery.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621006/pdf/KTIB_10_2017226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Metformin-dependent variation of microglia phenotype dictates pericytes maturation under oxygen-glucose deprivation. 二甲双胍依赖性小胶质细胞表型的变化决定了氧-葡萄糖剥夺下周细胞的成熟。
IF 3.1
Tissue Barriers Pub Date : 2022-10-02 DOI: 10.1080/21688370.2021.2018928
Mohammad Hossein Geranmayeh, Reza Rahbarghazi, Nazli Saeedi, Mehdi Farhoudi
{"title":"Metformin-dependent variation of microglia phenotype dictates pericytes maturation under oxygen-glucose deprivation.","authors":"Mohammad Hossein Geranmayeh,&nbsp;Reza Rahbarghazi,&nbsp;Nazli Saeedi,&nbsp;Mehdi Farhoudi","doi":"10.1080/21688370.2021.2018928","DOIUrl":"https://doi.org/10.1080/21688370.2021.2018928","url":null,"abstract":"<p><p>Blood-brain barrier resident cells are in the frontline of vascular diseases. To maintain brain tissue homeostasis, a series of cells are integrated regularly to form the neurovascular unit. It is thought that microglia can switch between M1/M2 phenotypes after the initiation of different pathologies. The existence of transition between maturity and stemness features in pericytes could maintain blood-brain barrier functionality against different pathologies. In the current study, the effect of metformin on the balance of the M1/M2 microglial phenotype under oxygen-glucose deprivation conditions and the impact of microglial phenotype changes on pericyte maturation have been explored. Both microglia and pericytes were isolated from the rat brain. Data showed that microglia treatment with metformin under glucose- and oxygen-free conditions suppressed microglia shifting into the M2 phenotype (CD206+ cells) compared to the control (<i>p</i> < .01) and metformin-treated groups (<i>p</i> < .05). Incubation of pericytes with microglia-conditioned media pretreated with metformin under glucose- and oxygen-free conditions or normal conditions increased pericyte maturity. These changes coincided with the reduction of the Sox2/NG2 ratio compared to the control pericytes (<i>p</i> < .05). Data revealed the close microglial-pericytic interplay under the ischemic and hypoxic conditions and the importance of microglial phenotype acquisition on pericyte maturation.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620990/pdf/KTIB_10_2018928.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10484161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review. 细胞穿透肽对微生物的生物治疗作用研究进展。
IF 3.1
Tissue Barriers Pub Date : 2022-07-03 Epub Date: 2021-10-25 DOI: 10.1080/21688370.2021.1995285
Idris Zubairu Sadiq, Aliyu Muhammad, Sanusi Bello Mada, Bashiru Ibrahim, Umar Aliyu Umar
{"title":"Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review.","authors":"Idris Zubairu Sadiq,&nbsp;Aliyu Muhammad,&nbsp;Sanusi Bello Mada,&nbsp;Bashiru Ibrahim,&nbsp;Umar Aliyu Umar","doi":"10.1080/21688370.2021.1995285","DOIUrl":"https://doi.org/10.1080/21688370.2021.1995285","url":null,"abstract":"<p><p>Selective permeability of biological membranes represents a significant barrier to the delivery of therapeutic substances into both microorganisms and mammalian cells, restricting the access of drugs into intracellular pathogens. Cell-penetrating peptides usually 5-30 amino acids with the characteristic ability to penetrate biological membranes have emerged as promising antimicrobial agents for treating infections as well as an effective delivery modality for biological conjugates such as nucleic acids, drugs, vaccines, nanoparticles, and therapeutic antibodies. However, several factors such as antimicrobial resistance and poor drug delivery of the existing medications justify the urgent need for developing a new class of antimicrobials. Herein, we review cell-penetrating peptides (CPPs) used to treat microbial infections. Although these peptides are biologically active for infections, effective transduction into membranes and cargo transport, serum stability, and half-life must be improved for optimum functions and development of next-generation antimicrobial agents.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359368/pdf/KTIB_10_1995285.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39558381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Epithelial integrity, junctional complexes, and biomarkers associated with intestinal functions. 上皮完整性、连接复合物和与肠道功能相关的生物标志物。
IF 3.1
Tissue Barriers Pub Date : 2022-07-03 Epub Date: 2021-10-30 DOI: 10.1080/21688370.2021.1996830
Arash Alizadeh, Peyman Akbari, Johan Garssen, Johanna Fink-Gremmels, Saskia Braber
{"title":"Epithelial integrity, junctional complexes, and biomarkers associated with intestinal functions.","authors":"Arash Alizadeh,&nbsp;Peyman Akbari,&nbsp;Johan Garssen,&nbsp;Johanna Fink-Gremmels,&nbsp;Saskia Braber","doi":"10.1080/21688370.2021.1996830","DOIUrl":"https://doi.org/10.1080/21688370.2021.1996830","url":null,"abstract":"<p><p>An intact intestinal barrier is crucial for immune homeostasis and its impairment activates the immune system and may result in chronic inflammation. The epithelial cells of the intestinal barrier are connected by tight junctions, which form an anastomosing network sealing adjacent epithelial cells. Tight junctions are composed of transmembrane and cytoplasmic scaffolding proteins. Transmembrane tight junction proteins at the apical-lateral membrane of the cell consist of occludin, claudins, junctional adhesion molecules, and tricellulin. Cytoplasmic scaffolding proteins, including zonula occludens, cingulin and afadin, provide a direct link between transmembrane tight junction proteins and the intracellular cytoskeleton. Each individual component of the tight junction network closely interacts with each other to form an efficient intestinal barrier. This review aims to describe the molecular structure of intestinal epithelial tight junction proteins and to characterize their organization and interaction. Moreover, clinically important biomarkers associated with impairment of gastrointestinal integrity are discussed.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/1a/KTIB_10_1996830.PMC9359365.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39844192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 18
Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on SARS-CoV-2 infection. 生物信息学分析揭示了SARS-CoV-2感染时肺上皮细胞的细胞屏障连接调节。
IF 3.1
Tissue Barriers Pub Date : 2022-07-03 Epub Date: 2021-11-05 DOI: 10.1080/21688370.2021.2000300
Mir S Adil, Daulat Khulood, S Priya Narayanan, Payaningal R Somanath
{"title":"Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on SARS-CoV-2 infection.","authors":"Mir S Adil,&nbsp;Daulat Khulood,&nbsp;S Priya Narayanan,&nbsp;Payaningal R Somanath","doi":"10.1080/21688370.2021.2000300","DOIUrl":"https://doi.org/10.1080/21688370.2021.2000300","url":null,"abstract":"<p><p>Cell junctions maintain the blood-tissue barriers to preserve vascular and tissue integrity. Viral infections reportedly modulate cell-cell junctions to facilitate their invasion. However, information on the effect of COVID-19 infection on the gene expression of cell junction and cytoskeletal proteins is limited. Using the Gene Expression Omnibus and Reactome databases, we analyzed the data on human lung A549, NHBE, and Calu-3 cells for the expression changes in cell junction and cytoskeletal proteins by SARS-CoV-2 (CoV-2) infection. The analysis revealed changes in 3,660 genes in A549, 100 genes in NHBE, and 592 genes in Calu-3 cells with CoV-2 infection. Interestingly, EGOT (9.8-, 3- and 8.3-fold; <i>p</i> < .05) and CSF3 (4.3-, 33- and 56.3-fold; <i>p</i> < .05) were the only two genes significantly elevated in all three cell lines (A549, NHBE and Calu-3, respectively). On the other hand, 39 genes related to cell junctions and cytoskeleton were modulated in lung cells, with DLL1 demonstrating alterations in all cells. Alterations were also seen in several miRNAs associated with the cell junction and cytoskeleton genes modulated in the analysis. Further, matrix metalloproteinases involved in disease pathologies, including MMP-3, -9, and -12 demonstrated elevated expression on CoV-2 infection (<i>p</i> < .05). The study findings emphasize the integral role of cell junction and cytoskeletal genes in COVID-19, suggesting their therapeutic potential. Our analysis also identified a distinct EGOT gene that has not been previously implicated in COVID-19. Further studies on these newly identified genes and miRNAs could lead to advances in the pathogenesis and therapeutics of COVID-19.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359367/pdf/KTIB_10_2000300.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39860723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Urinary IgG, serum CX3CL1 and miRNA-152-3p: as predictors of nephropathy in Egyptian type 2 diabetic patients. 尿IgG、血清CX3CL1和miRNA-152-3p:作为埃及2型糖尿病患者肾病的预测因子
IF 3.1
Tissue Barriers Pub Date : 2022-07-03 Epub Date: 2021-10-23 DOI: 10.1080/21688370.2021.1994823
Aml E Abdou, Haneya A A Anani, Hanan F Ibrahim, Eman Elshohat Ebrahem, Nora Seliem, Eman M I Youssef, Niveen M Ghoraba, Asmaa S Hassan, Marwa A A Ramadan, Eman Mahmoud, Shorouk Issa, Hend M Maghraby, Eman K Abdelrahman, Hala Ali Mohammed Hassan
{"title":"Urinary IgG, serum CX3CL1 and miRNA-152-3p: as predictors of nephropathy in Egyptian type 2 diabetic patients.","authors":"Aml E Abdou,&nbsp;Haneya A A Anani,&nbsp;Hanan F Ibrahim,&nbsp;Eman Elshohat Ebrahem,&nbsp;Nora Seliem,&nbsp;Eman M I Youssef,&nbsp;Niveen M Ghoraba,&nbsp;Asmaa S Hassan,&nbsp;Marwa A A Ramadan,&nbsp;Eman Mahmoud,&nbsp;Shorouk Issa,&nbsp;Hend M Maghraby,&nbsp;Eman K Abdelrahman,&nbsp;Hala Ali Mohammed Hassan","doi":"10.1080/21688370.2021.1994823","DOIUrl":"https://doi.org/10.1080/21688370.2021.1994823","url":null,"abstract":"<p><p>The purpose of this study was to assess the role of urinary IgG, serum CX3CL1 and miRNA 152-3p levels as predictors of nephropathy in type 2 Egyptian diabetic patients. Sixty type 2 diabetic patients and twenty healthy controls were enrolled in a cross-sectional study. Then they were grouped into: three groups based upon urine albumin excretion (UAE). The expression of miRNA 152-3p in serum was measured using quantitative polymerase chain reaction (RTq-PCR). Serum CX3CL1 and urinary IgG concentrations were measured by ELISA. RTq-PCR revealed that serum miRNA-152-3p levels in patients were significantly higher than in controls. There was significant differences between group with normoalbuminuria and groups with diabetic nephropathy DN as regard to age, duration of nephropathy, Albumin/Creatinine ratio (A/C ratio), creatinine, urine IgG, CX3CL1 and HbA1c. In diabetic patients, there was a significant positive correlation between miRNA-152-3p levels and disease duration only as well as significant positive correlations between urinary IgG levels and age, disease duration, serum creatinine, A/C ratio, and urea. Positive correlation between serum fractalkine CX3CL1 level and age, duration of disease, urea, creatinine, A/C ratio, HbA1C and IgG in patient with DN. Serum CX3CL1 level, urinary IgG were significantly increased with the progress of nephropathy so these integrated biomarkers could be used as good predictors for early identification of nephropathy. But miRNA- 152-3p has inadequate prognostic indicator for ESRD progression.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359404/pdf/KTIB_10_1994823.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39553925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
The Zonulin-transgenic mouse displays behavioral alterations ameliorated via depletion of the gut microbiota. zonulin转基因小鼠表现出通过消耗肠道微生物群而改善的行为改变。
IF 3.1
Tissue Barriers Pub Date : 2022-07-03 Epub Date: 2021-11-14 DOI: 10.1080/21688370.2021.2000299
Alba Miranda-Ribera, Gloria Serena, Jundi Liu, Alessio Fasano, Marcy A Kingsbury, Maria R Fiorentino
{"title":"The Zonulin-transgenic mouse displays behavioral alterations ameliorated via depletion of the gut microbiota.","authors":"Alba Miranda-Ribera,&nbsp;Gloria Serena,&nbsp;Jundi Liu,&nbsp;Alessio Fasano,&nbsp;Marcy A Kingsbury,&nbsp;Maria R Fiorentino","doi":"10.1080/21688370.2021.2000299","DOIUrl":"https://doi.org/10.1080/21688370.2021.2000299","url":null,"abstract":"<p><p>The gut-brain axis hypothesis suggests that interactions in the intestinal milieu are critically involved in regulating brain function. Several studies point to a gut-microbiota-brain connection linking an impaired intestinal barrier and altered gut microbiota composition to neurological disorders involving neuroinflammation. Increased gut permeability allows luminal antigens to cross the gut epithelium, and via the blood stream and an impaired blood-brain barrier (BBB) enters the brain impacting its function. Pre-haptoglobin 2 (pHP2), the precursor protein to mature HP2, is the first characterized member of the zonulin family of structurally related proteins. pHP 2 has been identified in humans as the thus far only endogenous regulator of epithelial and endothelial tight junctions (TJs). We have leveraged the Zonulin-transgenic mouse (Ztm) that expresses a murine pHP2 (zonulin) to determine the role of increased gut permeability and its synergy with a dysbiotic intestinal microbiota on brain function and behavior. Here we show that Ztm mice display sex-dependent behavioral abnormalities accompanied by altered gene expression of BBB TJs and increased expression of brain inflammatory genes. Antibiotic depletion of the gut microbiota in Ztm mice downregulated brain inflammatory markers ameliorating some anxiety-like behavior. Overall, we show that zonulin-dependent alterations in gut permeability and dysbiosis of the gut microbiota are associated with an altered BBB integrity, neuroinflammation, and behavioral changes that are partially ameliorated by microbiota depletion. Our results suggest the Ztm model as a tool for the study of the cross-talk between the microbiome/gut and the brain in the context of neurobehavioral/neuroinflammatory disorders.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359372/pdf/KTIB_10_2000299.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
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