scholarly journals Streptococcus gordoniiprograms epithelial cells to resist ZEB2 induction byPorphyromonas gingivalis

2019 ◽  
Vol 116 (17) ◽  
pp. 8544-8553 ◽  
Author(s):  
Jun Ohshima ◽  
Qian Wang ◽  
Zackary R. Fitzsimonds ◽  
Daniel P. Miller ◽  
Maryta N. Sztukowska ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Periodontal Diseases ◽  
Periodontal Pathogen ◽  
Community Partner ◽  
Microbial Composition ◽  
Mesenchymal Transition ◽  
Negative Regulatory Pathway ◽  
Host Signaling ◽  
Oral Epithelial

The polymicrobial microbiome of the oral cavity is a direct precursor of periodontal diseases, and changes in microhabitat or shifts in microbial composition may also be linked to oral squamous cell carcinoma. Dysbiotic oral epithelial responses provoked by individual organisms, and which underlie these diseases, are widely studied. However, organisms may influence community partner species through manipulation of epithelial cell responses, an aspect of the host microbiome interaction that is poorly understood. We report here thatPorphyromonas gingivalis, a keystone periodontal pathogen, can up-regulate expression of ZEB2, a transcription factor which controls epithelial–mesenchymal transition and inflammatory responses. ZEB2 regulation byP. gingivaliswas mediated through pathways involving β-catenin and FOXO1. Among the community partners ofP. gingivalis,Streptococcus gordoniiwas capable of antagonizing ZEB2 expression. Mechanistically,S. gordoniisuppressed FOXO1 by activating the TAK1-NLK negative regulatory pathway, even in the presence ofP. gingivalis. Collectively, these results establishS. gordoniias homeostatic commensal, capable of mitigating the activity of a more pathogenic organism through modulation of host signaling.

scholarly journals An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1060 ◽  
Author(s):  
Gastón Barbero ◽  
María Victoria Castro ◽  
María Belén Villanueva ◽  
María Josefina Quezada ◽  
Natalia Brenda Fernández ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Melanoma Cells ◽  
Dominant Negative ◽  
Migration And Invasion ◽  
Soluble Receptor ◽  
Mesenchymal Transition ◽  
Cytokines And Chemokines

Wnt5a signaling has been implicated in the progression of cancer by regulating multiple cellular processes, largely migration and invasion, epithelial-mesenchymal transition (EMT), and metastasis. Since Wnt5a signaling has also been involved in inflammatory processes in infectious and inflammatory diseases, we addressed the role of Wnt5a in regulating NF-κB, a pivotal mediator of inflammatory responses, in the context of cancer. The treatment of melanoma cells with Wnt5a induced phosphorylation of the NF-κB subunit p65 as well as IKK phosphorylation and IκB degradation. By using cDNA overexpression, RNA interference, and dominant negative mutants we determined that ROR1, Dvl2, and Akt (from the Wnt5a pathway) and TRAF2 and RIP (from the NF-κB pathway) are required for the Wnt5a/NF-κB crosstalk. Wnt5a also induced p65 nuclear translocation and increased NF-κB activity as evidenced by reporter assays and a NF-κB-specific upregulation of RelB, Bcl-2, and Cyclin D1. Further, stimulation of melanoma cells with Wnt5a increased the secretion of cytokines and chemokines, including IL-6, IL-8, IL-11, and IL-6 soluble receptor, MCP-1, and TNF soluble receptor I. The inhibition of endogenous Wnt5a demonstrated that an autocrine Wnt5a loop is a major regulator of the NF-κB pathway in melanoma. Taken together, these results indicate that Wnt5a activates the NF-κB pathway and has an immunomodulatory effect on melanoma through the secretion of cytokines and chemokines.

46. HIV-induced epithelial–mesenchymal transition in mucosal epithelium facilitates HPV paracellular penetration

Sexual Health ◽  
2013 ◽  
Vol 10 (6) ◽  
pp. 592 ◽  
Author(s):  
Sharof M. Tugizov ◽  
Rossana Herrera ◽  
Piri Veluppillai ◽  
Deborah Greenspan ◽  
Joel M. Palefsky
Keyword(s):  
Tight Junctions ◽  
Fluorescent Protein ◽  
Epithelial Mesenchymal Transition ◽  
Cell Junctions ◽  
Vimentin Expression ◽  
Hpv 16 ◽  
Mesenchymal Transition ◽  
Hiv Tat ◽  
Oral Epithelial ◽  
Oral Epithelia

Background The incidence of human papillomavirus (HPV)-associated epithelial lesions in HIV-infected individuals is substantially higher than in HIV-negative individuals. HIV may increase the risk of mucosal HPV infection by induction of an epithelial–mesenchymal transition (EMT) phenotype that leads to reduced epithelial barrier functions. Methods: To model the effect of EMT on HPV entry, we used oral epithelial biopsies, and oral and anal keratinocytes from HIV-infected and HIV-uninfected individuals. EMT was defined as loss of adherens and tight junctions, and induction of vimentin expression. To study epithelial HPV entry we used HPV-16 pseudovirions (PsVs) containing a plasmid expressing red fluorescent protein (RFP). PsV penetration was evaluated using confocal microscopy to detect RFP-generated fluorescence. Results: Compared with oral epithelia from HIV-uninfected individuals, oral epithelia from HIV-infected individuals had reduced adherens and tight junctions and expressed vimentin. Keratinocytes isolated from oral and anal tissues of HIV-infected individuals also showed loss of E-cadherin and induction of vimentin expression. Exposure of oral epithelial cells from HIV-uninfected individuals to HIV and HIV tat, gp120, and nef proteins induced EMT with reduced cell junctions and epithelial polarity, and allowed paracellular passage of HPV-16 PsV. Oral mucosal epithelial tissues treated with HIV tat and gp120 also lost tight junctions and allowed PsV paracellular penetration, leading to PsV entry into basal/parabasal cells. Conclusions: HIV-associated EMT in oral epithelia, and oral and anal keratinocytes leads to impaired barrier function. This facilitates entry of HPV/PsV into basal/parabasal cells, and may contribute to the increased incidence of HPV-associated malignancy in HIV-infected individuals.

scholarly journals A20 promotes melanoma progression via the activation of Akt pathway

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Jinyuan Ma ◽  
Huina Wang ◽  
Sen Guo ◽  
Xiuli Yi ◽  
Tao Zhao ◽  
...  
Keyword(s):  
Melanoma Cell ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Akt Pathway ◽  
Melanoma Metastasis ◽  
Mesenchymal Transition ◽  
Melanoma Progression ◽  
Cancer Pathogenesis

Abstract Melanoma is the most life-threatening skin cancer with increasing incidence around the world. Although recent advances in targeted therapy and immunotherapy have brought revolutionary progress of the treatment outcome, the survival of patients with advanced melanoma remains unoptimistic, and metastatic melanoma is still an incurable disease. Therefore, to further understand the mechanism underlying melanoma pathogenesis could be helpful for developing novel therapeutic strategy. A20 is a crucial ubiquitin-editing enzyme implicated immunity regulation, inflammatory responses and cancer pathogenesis. Herein, we report that A20 played an oncogenic role in melanoma. We first found that the expression of A20 was significantly up-regulated in melanoma cell lines. Then, we showed that knockdown of A20 suppressed melanoma cell proliferation in vitro and melanoma growth in vivo through the regulation of cell-cycle progression. Moreover, A20 could potentiate the invasive and migratory capacities of melanoma cell in vitro and melanoma metastasis in vivo by promoting epithelial–mesenchymal transition (EMT). Mechanistically, we found that Akt activation mediated the oncogenic effect of A20 on melanoma development, with the involvement of glycolysis. What’s more, the up-regulation of A20 conferred the acquired resistance to Vemurafenib in BRAF-mutant melanoma. Taken together, we demonstrated that up-regulated A20 promoted melanoma progression via the activation of Akt pathway, and that A20 could be exploited as a potential therapeutic target for melanoma treatment.

scholarly journals Role of Ubiquitin-Specific Peptidase 47 in Cancers and Other Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Kailing Pan ◽  
Junhao Fu ◽  
Wenxia Xu
Keyword(s):  
Neuronal Development ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Tumor Development ◽  
Post Translational Modifications ◽  
Mesenchymal Transition ◽  
Wide Range ◽  
Specific Protease ◽  
Range Of Functions ◽  
Targeted Inhibition

Deubiquitination is the reverse process of ubiquitination, which is catalyzed by deubiquitinase enzymes. More than 100 deubiquitinases have been identified. Ubiquitin-specific peptidase 47 (USP47), a member of the ubiquitin-specific protease family with high homology to USP7, is an active molecule with a wide range of functions and is closely associated with cancer and other diseases. However, no systematic summary exists regarding the functions of USP47. Here, we summarize the functions and expression regulation of USP47. USP47 is highly expressed in many tumors and is widely involved in tumor development, metastasis, drug resistance, epithelial-mesenchymal transition, and other processes. Targeted inhibition of USP47 can reverse malignant tumor behavior. USP47 also plays a role in inflammatory responses, myocardial infarction, and neuronal development. USP47 is involved in multiple levels of expression-regulating mechanisms, including transcriptional, post-transcriptional, and post-translational modifications. Development of targeted inhibitors against USP47 will provide a basis for studying the mechanisms of USP47 and developing therapeutic strategies for cancers and other diseases.

IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response

2009 ◽  
Vol 37 (4) ◽  
pp. 882-885 ◽  
Author(s):  
Angara Sureshbabu ◽  
Hiroshi Okajima ◽  
Daisuke Yamanaka ◽  
Surya Shastri ◽  
Elizabeth Tonner ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Replicative Senescence ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Fibrotic Response ◽  
Tissue Remodelling ◽  
Mesenchymal Transition ◽  
Fibroblast Activation

Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial–mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFβ1 (transforming growth factor-β1) induces both EMT and fibroblast activation and is considered to be a major pro-fibrotic factor. Recently, IGFBP-5 [IGF (insulin-like growth factor)-binding protein-5] has also been shown to induce similar effects on TGFβ1, and is strongly implicated in the process of senescence. It also stimulates migration of peripheral blood mononuclear cells, implicating it in the inflammatory response. In this paper, we examine the evidence for a role of IGFBP-5 in fibrosis and highlight its structural relationship with other matrix proteins and growth factors also implicated in tissue remodelling.

scholarly journals Activation of the Cholinergic Anti-inflammatory Pathway Attenuated Angiotension II-Dependent Hypertension and Renal Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Shu-jie Wu ◽  
Zhe-wei Shi ◽  
Xue Wang ◽  
Fang-fang Ren ◽  
Zuo-yi Xie ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Autonomic Control ◽  
Inflammatory Pathway ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Α7 Nachr ◽  
Induced Hypertension ◽  
Anti Inflammatory

Background: Angiotensin II (AngII) induces renal fibrosis, characterized by fibroblast proliferation, inflammatory cell infiltration and excessive extracellular matrix deposition, all of which was relevant closely to hypertension. The vagus nerve-related cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses. The aim of present study was to determine the effect of CAP on renal inflammation and fibrosis.Methods and Results: AngII-induced hypertension was induced in vivo by 14-days low-dose AngII infusion from osmotic minipumps. We used GTS-21 dihydrochloride, a selective nicotinic acetylcholine receptor agonist. Daily intraperitoneal GTS-21 injection and/or vagotomy started after hypertension was confirmed and continued for 4 weeks. The elevated blood pressure caused by AngII was significantly attenuated by GTS-21. Improved baroreflex sensitivity was observed after GTS-21 administration. Masson stain and immunoblotting revealed that deposition of excessive fibrosis and overexpression of inflammatory cytokines induced by AngII was reduced by GTS-21. To determine the role of autonomic control in CAP, unilateral vagotomy was performed. Vagotomy weakened the effect of CAP on AngII-induced hypertension. In vitro, GTS-21 suppressed NF-κB activation, attenuated AngII-induced epithelial-mesenchymal transition and reduced inflammation and fibrosis in NRK-52E cells; α-bungarotoxin (α-Bgt, an α7-nAChR selective antagonist) partly inhibited these effects.Conclusion: CAP protected against AngII-induced hypertension via improvement in autonomic control, suppression of NF-κB activation, and reduction of renal fibrosis and inflammatory response.

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