Epithelial maturity influences EPEC-induced desmosomal alterations

Roxas, Jennifer Lising; Vedantam, Gayatri; Viswanathan, V. K.

doi:10.1080/19490976.2018.1506669

Cited by 10 publications

(8 citation statements)

References 33 publications

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“…Although keratins are mainly known for their ability to strengthen and stabilize cells, they can indirectly influence intercellular adhesion. The latter can be facilitated by clusters of desmosomal cadherins, supported by IF-made desmoplakins and plakophilins [34]. However, it is worth keeping in mind that the confluence of cultured cells, and thus number of cell junctions, increases along the culture time [35], which may prove to be an alternative explanation for increased KRT18 expression.…”

Section: Discussionmentioning

confidence: 99%

“Biological Adhesion” is a Significantly Regulated Molecular Process during Long-Term Primary In Vitro Culture of Oviductal Epithelial Cells (Oecs): A Transcriptomic and Proteomic Study

Budna‐Tukan

Światły-Błaszkiewicz

Celichowski

et al. 2019

IJMS

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Oviductal epithelial cells (OECs) actively produce stimulating and protecting factors, favoring survival and viability of gametes and early embryos. The oviduct participates in the initial reproductive events, which strongly depends on adhesion. The analysis of differential gene expression in OECs, during long-term in vitro culture, enables recognition of new molecular markers regulating several processes, including “biological adhesion”. Porcine oviducts were stained with hematoxylin and eosin, as well as with antibodies against epithelial markers. Then, OECs were long-term in vitro cultured and after 24 h, 7, 15, and 30 days of culture were subjected to transcriptomic and proteomic assays. Microarrays were employed to evaluate gene expression, with Matrix-assisted laser desorption/ionization-time of light (MALDI-TOF) mass spectrometry applied to determine the proteome. The results revealed proper morphology of the oviducts and typical epithelial structure of OECs during the culture. From the set of differentially expressed genes (DEGs), we have selected the 130 that encoded proteins detected by MALDI-TOF MS analysis. From this gene pool, 18 significantly enriched gene ontology biological processes (GO BP) terms were extracted. Among them we focused on genes belonging to “biological adhesion” GO BP. It is suggested that increased expression of studied genes can be attributed to the process of intensive secretion of substances that exhibit favorable influence on oviductal environment, which prime gametes adhesion and viability, fertilization, and early embryo journey.

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Section: Discussionmentioning

confidence: 99%

“Biological Adhesion” is a Significantly Regulated Molecular Process during Long-Term Primary In Vitro Culture of Oviductal Epithelial Cells (Oecs): A Transcriptomic and Proteomic Study

Budna‐Tukan

Światły-Błaszkiewicz

Celichowski

et al. 2019

IJMS

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“…The importance of desmosomes during disease pathogenesis is not limited to IBD, as it also plays a critical role in enteropathogenic Escherichia coli (EPEC) infection. 100,101 Infection of enterocytes with EPEC reduced Dsg2 and Dsc2 levels in vitro and disruption of desmosomes even preceded ultrastructural alterations of TJs in mice in vivo. In this scenario, the proposed mechanism was a Rho GTPase-and actin-mediated dysregulation of desmosomes via the EHEC toxin EspH, which can sequester p115-RhoGEF and thereby reduce RhoA activity.…”

Section: Levels and Desmosome Ultrastructure In Ibdmentioning

confidence: 98%

“…The importance of desmosomes during disease pathogenesis is not limited to IBD, as it also plays a critical role in enteropathogenic Escherichia coli (EPEC) infection 100,101 . Infection of enterocytes with EPEC reduced Dsg2 and Dsc2 levels in vitro and disruption of desmosomes even preceded ultrastructural alterations of TJs in mice in vivo.…”

Section: Alterations Of Dsg2 Levels and Desmosome Ultrastructure In Ibdmentioning

confidence: 99%

Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

2020

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Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and Ulcerative colitis (UC) have a complex and multifactorial pathogenesis which is incompletely understood. A typical feature closely associated with clinical symptoms is impaired intestinal epithelial barrier function. Mounting evidence suggests that desmosomes, which together with tight junctions (TJ) and adherens junctions (AJ) form the intestinal epithelial barrier, play a distinct role in IBD pathogenesis. This is based on the finding that desmoglein (Dsg) 2, a cadherin‐type adhesion molecule of desmosomes, is required for maintenance of intestinal barrier properties both in vitro and in vivo, presumably via Dsg2‐mediated regulation of TJ. Mice deficient for intestinal Dsg2 show increased basal permeability and are highly susceptible to experimental colitis. In several cohorts of IBD patients, intestinal protein levels of Dsg2 are reduced and desmosome ultrastructure is altered suggesting that Dsg2 is involved in IBD pathogenesis. In addition to its adhesive function, Dsg2 contributes to enterocyte cohesion and intestinal barrier function. Dsg2 is also involved in enterocyte proliferation, barrier differentiation and induction of apoptosis, in part by regulation of p38MAPK and EGFR signalling. In IBD, the function of Dsg2 appears to be compromised via p38MAPK activation, which is a critical pathway for regulation of desmosomes and is associated with keratin phosphorylation in IBD patients. In this review, the current findings on the role of Dsg2 as a novel promising target to prevent loss of intestinal barrier function in IBD patients are discussed.

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“…The type 1 pilus adhesin (FimH) expressed by UPEC binds hDsg2 to establish kidney infection in male C3H/HeN mice [ 43 ]. EPEC disrupts desmosomes, weakens cell–cell adhesion and perturbs barrier function of intestinal epithelial cells, which involves a cellular redistribution of hDsg2 during infection [ 44 ]. Pathogen-induced cleavage of desmogleins has previously been shown for hDsg1.…”

Section: Discussionmentioning

confidence: 99%

Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells

et al. 2021

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Background High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesions are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism of H. pylori interference with the epithelial barrier integrity. Results Using a proteomic approach we identified human desmoglein-2 (hDsg2), neuropilin-1, ephrin-B2, and semaphorin-4D as novel extracellular HpHtrA substrates and confirmed the well characterized target hCdh1. HpHtrA-mediated hDsg2 cleavage was further analyzed by in vitro cleavage assays using recombinant proteins. In infection experiments, we demonstrated hDsg2 shedding from H. pylori-colonized MKN28 and NCI-N87 cells independently of pathogen-induced matrix-metalloproteases or ADAM10 and ADAM17. Conclusions Characterizing the substrate specificity of HpHtrA revealed efficient hDsg2 cleavage underlining the importance of HpHtrA in opening intercellular junctions.

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Epithelial maturity influences EPEC-induced desmosomal alterations

Cited by 10 publications

References 33 publications

“Biological Adhesion” is a Significantly Regulated Molecular Process during Long-Term Primary In Vitro Culture of Oviductal Epithelial Cells (Oecs): A Transcriptomic and Proteomic Study

“Biological Adhesion” is a Significantly Regulated Molecular Process during Long-Term Primary In Vitro Culture of Oviductal Epithelial Cells (Oecs): A Transcriptomic and Proteomic Study

Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells

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