scholarly journals Colon epithelial cell TGFβ signaling modulates the expression of tight junction proteins and barrier function in mice

2021 ◽  
Author(s):  
Paula Marincola Smith ◽  
Yash A Choksi ◽  
Nicholas O Markham ◽  
David N Hanna ◽  
Jinghuan Zi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Tight Junction ◽  
Barrier Function ◽  
Protein Translation ◽  
Tight Junction Proteins ◽  
Tgfβ Signaling ◽  
Mouse Colon ◽  
Junction Proteins

Background: Defective barrier function is a predisposing factor in inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). While TGFβ signaling defects have been associated with IBD and CAC, few studies have examined the relationship between TGFβ and intestinal barrier function. Here, we examine the role of TGFβ signaling via SMAD4 in modulation of colon barrier function. Methods: The Smad4 gene was conditionally deleted in the intestines of adult mice and intestinal permeability assessed using an in vivo 4kD FITC-Dextran (FD4) permeability assay. Mouse colon was isolated for gene expression (RNA-sequencing), western blot, and immunofluorescence analysis. In vitro colon organoid culture was utilized to assess junction-related gene expression by qPCR and trans-epithelial resistance (TER). In silico analyses of human IBD and colon cancer databases were performed. Results: Mice lacking intestinal expression of Smad4 demonstrate increased colonic permeability to FD4 without gross mucosal damage. mRNA/protein expression analyses demonstrate significant increases in Cldn2/Claudin 2 and Cldn8/Claudin 8, and decreases in Cldn3, Cldn4, and Cldn7/Claudin 7 with intestinal SMAD4 loss in vivo without changes in Claudin protein localization. TGFb1/BMP2 treatment of polarized SMAD4+ colonoids increases TER. Cldn2, Cldn4, Cldn7, and Cldn8 are regulated by canonical TGFβ signaling, and TGFβ-dependent regulation of these genes is dependent on nascent RNA transcription (Cldn2, Cldn4, Cldn8) but not nascent protein translation (Cldn4, Cldn8). Human IBD/colon cancer specimens demonstrate decreased SMAD4, CLDN4, CLDN7, and CLDN8 and increased CLDN2 compared to healthy controls. Conclusion: Canonical TGFβ signaling modulates the expression of tight junction proteins and barrier function in mouse colon.

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

2017 ◽  
Vol 95 (3) ◽  
pp. 1313 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle1

2017 ◽  
Vol 95 (3) ◽  
pp. 1313-1324 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins

scholarly journals Regulation of testicular tight junctions by gonadotrophins in the adult Djungarian hamster in vivo

Reproduction ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 867-877 ◽  
Author(s):  
Gerard A Tarulli ◽  
Sarah J Meachem ◽  
Stefan Schlatt ◽  
Peter G Stanton
Keyword(s):  
Tight Junction ◽  
Adaptor Protein ◽  
Tight Junction Protein ◽  
Mrna Levels ◽  
Tight Junction Proteins ◽  
Djungarian Hamster ◽  
Junction Protein ◽  
Protein Localisation ◽  
Junction Proteins

This study aimed to assess the effect of gonadotrophin suppression and FSH replacement on testicular tight junction dynamics and blood–testis barrier (BTB) organisation in vivo, utilising the seasonal breeding Djungarian hamster. Confocal immunohistology was used to assess the cellular organisation of tight junction proteins and real-time PCR to quantify tight junction mRNA. The effect of tight junction protein organisation on the BTB permeability was also investigated using a biotin-linked tracer. Tight junction protein (claudin-3, junctional adhesion molecule (JAM)-A and occludin) localisation was present but disorganised after gonadotrophin suppression, while mRNA levels (claudin-11, claudin-3 and occludin) were significantly (two- to threefold) increased. By contrast, both protein localisation and mRNA levels for the adaptor protein zona occludens-1 decreased after gonadotrophin suppression. FSH replacement induced a rapid reorganisation of tight junction protein localisation. The functionality of the BTB (as inferred by biotin tracer permeation) was found to be strongly associated with the organisation and localisation of claudin-11. Surprisingly, JAM-A was also recognised on spermatogonia, suggesting an additional novel role for this protein in trans-epithelial migration of germ cells across the BTB. It is concluded that gonadotrophin regulation of tight junction proteins forming the BTB occurs primarily at the level of protein organisation and not gene transcription in this species, and that immunolocalisation of the organised tight junction protein claudin-11 correlates with BTB functionality.

Differential gene expression of tight-junction proteins and their correlation with PRSS8 and prognosis in colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15548-e15548
Author(s):  
Wancai Yang ◽  
Yongchen Guo ◽  
Jim Lu ◽  
Yonghua Bao
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Tight Junction ◽  
Early Onset ◽  
Normal Mucosa ◽  
Colorectal Carcinogenesis ◽  
Tight Junction Proteins ◽  
Intestinal Epithelia ◽  
Differential Gene ◽  
Junction Proteins

e15548 Background: Intestinal epithelia cells are made up of tight junctions, adheren junctions and desmosomes. As integral membrane proteins, the tight junction proteins (TJPs) claudins (CLDNs) and occludin (OCLN) are the most important TJPs that play a major role in maintaining the integrity of the intestinal epithelia and regulate several key signaling pathways in cancers. Dysregulation of tight junction and adheren junction has been shown to be associated with disruption of mucosa barriers, chronic colitis, early onset of colorectal carcinogenesis, epithelial mesenchymal transition and cancer metastasis. Our recent studies have shown that intestinal conditional knockout of the Press8 (protease serine 8) gene causes disruption of intestinal epithelial homeostasis, spontaneous inflammation and tumorigenesis in mouse intestine. Whether these pathogeneses are resulted from TJPs alterations and their correlation with PRSS8 are largely unknown. Methods: PRSS8 overexpression plasmid was transfected into colon cancer cell line HCT116 cells and proteomics was conducted. The Cancer Genome Atlas colorectal cancer (CRC) data set was deeply mined, and the correlation between TJPs’ alterations, PRSS8 and prognosis was analyzed. Results: In vitro proteomics assay showed that increasing expression of PRSS8 led to differential expression of cellular TJPs and adheren proteins, including upregulation of E-cadherin, TJP1 (ZO-1) and OCLN, and downregulation of RAC1, CDC42, RHOA, CLDND1, ARHGAP1, CTNNB1 and CTNNBL1. TCGA data mining showed differential gene expression of tight junction proteins. For instance, similar as PRSS8, most colonic mucosal TJPs, such as TJP1 (ZO-1), TJP3, OLCN, CLDN7, CLDN8 and PTPRJ, were significantly decreased in CRC tissues (n = 215), compared to normal mucosa (n = 22). Moreover, these reduced expression of TJPs were positively correlated with the reduction of PRSS8 and were inversely associated with prognosis. In contrast, another group of TJPs, such as TJP2, CLDN1, CLDN2 and CLDN12, was significantly increased in CRC tissues in comparison with the normal mucosa. These increases of expression were negatively correlated with PRSS8 expression and poor outcomes. More interestingly, the PTPRJ, a newly identified tumor suppressor, was dramatically reduced in metastatic CRC, compared to the primary CRC. Furthermore, the reduced expression of PTPRJ was linked to poor prognosis in the CRC patients. The underlying mechanisms of regulatory interaction between PRSS8 and TJPs are under investigation. Conclusions: TJPs are differentially expressed in CRC and the alterations were well correlated with PRSS8 and prognosis. Therefore, these two opposite groups of TJPs could be used as biomarkers for the monitoring of early onset colorectal carcinogenesis, progression and for the prediction of prognosis.

Chronic adrenomedullin treatment improves blood-brain barrier function but has no effects on expression of tight junction proteins

2003 ◽  
pp. 565-568 ◽  
Author(s):  
Bela Kis ◽  
J. A. Snipes ◽  
M. A. Deli ◽  
C. S. Ábrahám ◽  
H. Yamashita ◽  
...  
Keyword(s):  
Tight Junction ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Blood Brain ◽  
Junction Proteins
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