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E- and VE-cadherin processing in epithelial cells. A431 cells were incubated for the indicated times in the absence (non-treated, NT) or presence of 1 µM staurosporin (STS) or 5 µM ionomycin (IONO). The blots show the expression of full-length (FL, 130 kDa upper bands), CTF1 (37 kDa middle bands) and CTF2 (28 kDa bottom bands) of E-cadherin (a) and VE-cadherin (b). Results are representative of 4 independent experiments. Different blot exposures were used in Figs. 1-3 and Supplementary Fig. 1 to facilitate the visualization of FL cadherins (short exposures, short exp.), as well as CTF1 fragments and CTF2 fragments (long exposures, long exp.), as indicated.
Source publication
Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by H2O2 exposure induced effi...
Citations
... Repeated reactivation of HSV-1 may lead to excessive production of reactive oxygen species (ROS), 62 thereby inducing OS. 63 ROS upregulate ɣ-secretase and BACE-1, increasing Aβ production and impairing its clearance. [64][65][66] Simultaneously, protein oxidative damage caused by OS promotes tau self-aggregation, accelerating the formation of NFTs. 67,68 Furthermore, the CNS is particularly vulnerable to OS, 69,70 leading to impaired neuronal function and reduced survival rates, ultimately potentially contributing to AD. 71,72 The APOE-ε4 gene is the most common genetic risk factor for AD. ...
Background
Recently, some studies suggested that Herpes simplex virus type 1 (HSV-1) infection is an important environmental factor for Alzheimer’s disease(AD). The literature on research about HSV-1 infection and AD is emerging. This study used the bibliometric method to investigate the relationship between HSV-1 infection and AD.
Methods
We searched the Web of Science Core Collection for relevant literature on AD and HSV-1 from 1990 to 2024. Bibliometric and visualization analyses were performed using VOSviewer and CiteSpace.
Results
From 1990 to 2024, the number of publications showed an increasing trend. The United States made the largest contributions in productivity. The University of Manchester was the most productive organization. Professor Ruth F. Itzhaki was the most influential researcher. The Journal of Alzheimer’s Disease had published the most articles. Research on the mechanisms by which HSV infection contributes to AD remains a hotspot in the field, and future studies may further focus on antiviral therapeutic strategies targeting HSV-1 infection.
Conclusion
Our analysis provides basic information about research in AD and HSV-1. The current research hotspots in this field mainly include the mechanism of AD caused by HSV-1, and antiviral drugs to treat or prevent AD.
... β-catenin is a transcription factor that is normally degraded by the APC/axin/GSK-3β complex [34,35]. However, β-catenin is also found to bind to the cytoplasmic domain of E-cadherin, and BFT-induced E-cadherin cleavage can result in the translocation of β-catenin to the nucleus [17]. The translocated β-catenin can activate IL-8 expression [36]. ...
Enterotoxigenic Bacteroides fragilis (ETBF) is an intestinal bacterium that secretes the metalloprotease Bacteroides fragilis toxin (BFT), which induces E-cadherin cleavage and interleukin-8 secretion in human intestinal epithelial cell lines. ETBF-induced E-cadherin cleavage is proposed to be the underlying reason for the promotion of colitis in ETBF-infected mice. However, a BFT-responsive murine cell line has not yet been reported. In the current study, we report that the mouse colonic epithelial cell line CMT93 undergoes E-cadherin ectodomain cleavage, cell rounding, and proliferation in response to BFT treatment. The amino acid sequence of the putative cleavage site of E-cadherin is identical in both BFT-responsive (CMT93) and BFT-nonresponsive (MSIE, CT26, YAMC, and B16) cell lines, suggesting that the E-cadherin amino acid sequence is not responsible for this observation. After E-cadherin ectodomain cleavage, the membrane-bound intracellular E-cadherin domain underwent cleavage by γ-secretase and was subsequently degraded by the proteasome. Moreover, BFT induced the secretion of two chemokines (LIX and KC) and the formation of soluble TNFR1 in the CMT93 cell line. The identification of a BFT-responsive murine cell line may be used to elucidate the mechanism of ETBF pathogenesis in ETBF murine infection models.
... Generally, Cdh1 expression on the surface of epithelial cells is highly dynamic and dysfunctional cadherin molecules are rapidly internalized and removed via the 26S proteasome system [29]. Therefore, cells immediately re-express Cdh1 to re-establish intercellular adhesions. ...
Impaired E-cadherin (Cdh1) functions are closely associated with cellular dedifferentiation, infiltrative tumor growth and metastasis, particularly in gastric cancer. The class-I carcinogen Helicobacter pylori (H. pylori) colonizes gastric epithelial cells and induces Cdh1 shedding, which is primarily mediated by the secreted bacterial protease high temperature requirement A (HtrA). In this study, we used human primary epithelial cell lines derived from gastroids and mucosoids from different healthy donors to investigate HtrA-mediated Cdh1 cleavage and the subsequent impact on bacterial pathogenesis in a non-neoplastic context. We found a severe impairment of Cdh1 functions by HtrA-induced ectodomain cleavage in 2D primary cells and mucosoids. Since mucosoids exhibit an intact apico-basal polarity, we investigated bacterial transmigration across the monolayer, which was partially depolarized by HtrA, as indicated by microscopy, the analyses of the transepithelial electrical resistance (TEER) and colony forming unit (cfu) assays. Finally, we investigated CagA injection and observed efficient CagA translocation and tyrosine phosphorylation in 2D primary cells and, to a lesser extent, similar effects in mucosoids. In summary, HtrA is a crucially important factor promoting the multistep pathogenesis of H. pylori in non-transformed primary gastric epithelial cells and organoid-based epithelial models.
BACKGROUND
Endogenous regeneration of pancreatic islet β-cells is a path to cure both type 1 and advanced type 2 diabetes. Pancreatic cancer cell line-1 (PANC-1), a human pancreatic islet progenitor cell line, can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates (ILAs). However, the underlying mechanism has not been explored.
AIM
To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.
METHODS
PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulin-secreting cells. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.
RESULTS
The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3, which specifically phosphorylated the Ser655/Thr658 site of α-catenin in the cadherin-catenin complex, participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.
CONCLUSION
The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells, providing a novel approach for endogenous islet β-cell regeneration.
