T cell protein tyrosine phosphatase protects intestinal barrier function by restricting epithelial tight junction remodeling

Marchelletta, Ronald R.; Krishnan, Moorthy; Spalinger, Marianne R.; Placone, Taylaur W.; Alvarez, Rocio; Sayoc-Becerra, Anica; Canale, Vinicius; Shawki, Ali; Park, Young Su; Bernts, Lucas H P; Myers, Stephen P; Tremblay, Michel L.; Barrett, Kim E.; Krystofiak, Evan; Kachar, Bechara; McGovern, Dermot; Weber, Christopher; Hanson, Elaine; Eckmann, Lars; McCole, Declan F.

doi:10.1172/jci138230

Cited by 20 publications

(19 citation statements)

References 69 publications

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“…Experiments in cultured cells suggested that ZO-1 expression could be directly modulated by GATA6 [ 59 ]. Recently, Marchelletta and colleagues reported that the impaired function of T cell protein tyrosine phosphatase (TCPTP), encoded by the protein tyrosine phosphatase non-receptor type 2 ( PTPN2 ) gene, contributed to the epithelial tight junction protein remodeling and increased intestinal permeability [ 66 ]. In particular, Tcptp -deficient mice showed increased claudin-2 expression, intestinal permeability, and inflammatory cytokine production [ 66 ].…”

Section: Breaking the Balance: Intestinal Barrier Dysfunction And Gut...mentioning

confidence: 99%

“…Recently, Marchelletta and colleagues reported that the impaired function of T cell protein tyrosine phosphatase (TCPTP), encoded by the protein tyrosine phosphatase non-receptor type 2 ( PTPN2 ) gene, contributed to the epithelial tight junction protein remodeling and increased intestinal permeability [ 66 ]. In particular, Tcptp -deficient mice showed increased claudin-2 expression, intestinal permeability, and inflammatory cytokine production [ 66 ]. In detail, TCPTP was able to maintain the localization of ZO-1 and occludin at apical tight junctions, as well as to modulate the turn-over of claudin-2, a cation pore-forming transmembrane protein, by upregulating the serine metalloproteinase matriptase, which promoted claudin-2 proteosomal degradation [ 66 ].…”

Section: Breaking the Balance: Intestinal Barrier Dysfunction And Gut...mentioning

confidence: 99%

“…In particular, Tcptp -deficient mice showed increased claudin-2 expression, intestinal permeability, and inflammatory cytokine production [ 66 ]. In detail, TCPTP was able to maintain the localization of ZO-1 and occludin at apical tight junctions, as well as to modulate the turn-over of claudin-2, a cation pore-forming transmembrane protein, by upregulating the serine metalloproteinase matriptase, which promoted claudin-2 proteosomal degradation [ 66 ].…”

Section: Breaking the Balance: Intestinal Barrier Dysfunction And Gut...mentioning

confidence: 99%

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Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases

et al. 2022

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The intestinal mucosal barrier, also referred to as intestinal barrier, is widely recognized as a critical player in gut homeostasis maintenance as it ensures the complex crosstalk between gut microbes (both commensals and pathogens) and the host immune system. Highly specialized epithelial cells constantly cope with several protective and harmful agents to maintain the multiple physiological functions of the barrier as well as its integrity. However, both genetic defects and environmental factors can break such equilibrium, thus promoting gut dysbiosis, dysregulated immune-inflammatory responses, and even the development of chronic pathological conditions. Here, we review and discuss the molecular and cellular pathways underlying intestinal barrier structural and functional homeostasis, focusing on potential alterations that may undermine this fine balance.

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Section: Breaking the Balance: Intestinal Barrier Dysfunction And Gut...mentioning

confidence: 99%

Section: Breaking the Balance: Intestinal Barrier Dysfunction And Gut...mentioning

confidence: 99%

Section: Breaking the Balance: Intestinal Barrier Dysfunction And Gut...mentioning

confidence: 99%

See 1 more Smart Citation

Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases

et al. 2022

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“…Changes in the expression and distribution of claudin-2, -5, and -8 lead to discontinuous TJs and barrier dysfunction in active CD [ 26 , 106 ]. Loss-of-function mutations in protein tyrosine phosphatase nonreceptor type 2 [ 109 ] increase the risk of IBD and celiac disease. Interestingly, T-cell protein tyrosine phosphatase (TCPTP) protects against intestinal barrier dysfunction induced by the inflammatory cytokine IFN-gamma.…”

Section: Novel Roles Of Vitamin D Vdr and Tjs In Diseasesmentioning

confidence: 99%

“…Interestingly, T-cell protein tyrosine phosphatase (TCPTP) protects against intestinal barrier dysfunction induced by the inflammatory cytokine IFN-gamma. The mechanisms are that it maintained localization of ZO-1 and occludin at apical tight junctions and restricted both expression and insertion of the cation pore-forming transmembrane protein, claudin-2, at TJs through upregulation of matriptase, the inhibitory cysteine protease, in experimental mouse models [ 109 ].…”

Section: Novel Roles Of Vitamin D Vdr and Tjs In Diseasesmentioning

confidence: 99%

Vitamin D Receptor Influences Intestinal Barriers in Health and Disease

Sun

Zhang

2022

Cells

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Vitamin D receptor (VDR) executes most of the biological functions of vitamin D. Beyond this, VDR is a transcriptional factor regulating the expression levels of many target genes, such as genes for tight junction proteins claudin-2, -5, -12, and -15. In this review, we discuss the progress of research on VDR that influences intestinal barriers in health and disease. We searched PubMed and Google Scholar using key words vitamin D, VDR, tight junctions, cancer, inflammation, and infection. We summarize the literature and progress reports on VDR regulation of tight junction distribution, cellular functions, and mechanisms (directly or indirectly). We review the impacts of VDR on barriers in various diseases, e.g., colon cancer, infection, inflammatory bowel disease, and chronic inflammatory lung diseases. We also discuss the limits of current studies and future directions. Deeper understanding of the mechanisms by which the VDR signaling regulates intestinal barrier functions allow us to develop efficient and effective therapeutic strategies based on levels of tight junction proteins and vitamin D/VDR statuses for human diseases.

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