The actin-bundling protein Fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair

Qualtrough, David; Smallwood, Katie; Littlejohns, D. W.; Pignatelli, Massimo

doi:10.1186/1471-230x-11-14

Cited by 16 publications

(12 citation statements)

References 25 publications

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“…Rifaximin-mediated reduction of RbAp48 further suggested that cytoprotection was likely due do modifications to the expression levels of proteins associated with the cytoskeleton and cellular integrity. This observation is further supported by the observation that fascin, an organizational protein that bundles actin in cells [38] and highly expressed in colorectal adenocarcinomas and in patients with inflammatory bowel disease [3], [38] was up-regulated following rifaximin treatment.…”

Section: Discussionmentioning

confidence: 54%

Rifaximin-Mediated Changes to the Epithelial Cell Proteome: 2-D Gel Analysis

et al. 2013

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Rifaximin is a semi-synthetic rifamycin derivative that is used to treat different conditions including bacterial diarrhea and hepatic encephalopathy. Rifaximin is of particular interest because it is poorly adsorbed in the intestines and has minimal effect on colonic microflora. We previously demonstrated that rifaximin affected epithelial cell physiology by altering infectivity by enteric pathogens and baseline inflammation suggesting that rifaximin conferred cytoprotection against colonization and infection. Effects of rifaximin on epithelial cells were further examined by comparing the protein expression profile of cells pretreated with rifaximin, rifampin (control antibiotic), or media (untreated). Two-dimensional (2-D) gel electrophoresis identified 36 protein spots that were up- or down-regulated by over 1.7-fold in rifaximin treated cells compared to controls. 15 of these spots were down-regulated, including annexin A5, intestinal-type alkaline phosphatase, histone H4, and histone-binding protein RbbP4. 21 spots were up-regulated, including heat shock protein (HSP) 90α and fascin. Many of the identified proteins are associated with cell structure and cytoskeleton, transcription and translation, and cellular metabolism. These data suggested that in addition to its antimicrobial properties, rifaximin may alter host cell physiology that provides cytoprotective effects against bacterial pathogens.

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Section: Discussionmentioning

confidence: 54%

Rifaximin-Mediated Changes to the Epithelial Cell Proteome: 2-D Gel Analysis

et al. 2013

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“…Qualtrough observed a higher Fascin expression in colon tissues among patients with colitis ulcerosa and Leśniowski-Crohn disease [19]. The expression was increased especially in repaired tissues.…”

Section: Discussionmentioning

confidence: 79%

“…The expression was increased especially in repaired tissues. In neoplastic transformation, an increased Fascine expression correlates with poor survival [9,19]. UVB is a well-known factor that inhibits an immune response in dermis changing the antigen presenting cells' function and generating antigen tolerance in CD4+ cells.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of PDT in vulvar LS treatment based on immunohistochemical analysis of CD3, CD4, CD8, CD57, Granzyme B and Fascin expression

Olejek¹,

Olszak-Wąsik²,

Stęplewska³

et al. 2013

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155 SummaryBackground: Lichen sclerosus (LS) is an immune-mediated chronic dermatosis of perimenopausal women. Inflammatory infiltration has been suggested as a potential cause of LS changes in epidermis and dermis. Photodynamic therapy (PDT) is a specific noninvasive treatment based on detection and subsequent selective destruction of LS-affected tissues that are marked by a photosensitizer. Immunomodulatory and cytotoxic effects of PDT are responsible for inducing several immunologic reactions which leads to inflammatory condition improvement.The aim of the study was to determine the efficacy of photodynamic therapy for genital LS in correlation to protein expression involved in inflammatory infiltration -CD3, CD4, CD8, CD57, Granzyme B and Fascin.Material and methods: A group of patients has been treated for active LS disease, diagnosis was histologically confirmed in skin biopsies. The skin biopsies were taken and analyzed with antibodies: CD3, CD4, CD8, CD57, Granzyme B and Fascin before and after PDT treatment.Results: The study shows the efficacy of PDT in LS treatment including changes to CD3, CD4, CD57, Fascin, Granzyme B and the lymphocytic infiltration in skin sections. The proliferation index of CD4 did not differ before and after PDT.Conclusions: The PDT is a very effective therapeutic method in LS treatment. Key words: lichen sclerosus, vulvar, PDT. StreszczenieWstęp: Liszaj twardzinowy (LS) jest przewlekłą dermatozą z kręgu chorób immunologicznych spotykaną w grupie kobiet w wieku okołomenopauzalnym. W obrębie naskórka i skóry objętej zmianami o typie LS stwierdza się obecność nacieków zapalnych. Nieinwazyjną metodą leczenia tego schorzenia jest terapia fotodynamiczna (PDT), która dzięki zastosowaniu fotouczulacza pozwala na wykrycie i selektywne niszczenie obszarów tkanki zajętej liszajem twardzinowym. Immunomodulujące oraz cytotoksyczne efekty działania PDT są odpowiedzialne za wzbudzanie reakcji immunologicznych prowadzących do zmniejszenia stanu zapalnego.Cel pracy: Celem pracy była próba określenia efektywności PDT w przypadkach liszaja twardzinowego sromu w zależności od ekspresji związanych z procesem zapalnym: CD3, CD4, CD8, CD57, granzymu B oraz fascyny.Materiał i metody: Badaniem objęto grupę pacjentek z liszajem twardzinowym sromu, potwierdzonym w badaniu histopatologicznym wycinków ze sromu. W wycinkach tych oceniano ekspresję CD3, CD4, CD8, CD57, granzymu B oraz fascyny przed zastosowaniem PDT oraz po jej zastosowaniu.Wyniki: Wykazano zmniejszoną ekspresję CD3, CD8, CD57, fascyny i granzymu B po zastosowaniu terapii PTD oraz zmniejszenie nacieku limfocytarnego w wycinkach ze sromu. Indeks proliferacji CD4 nie różnił się istotnie przed zastosowaniem PDT i po jej zastosowaniu.Wnioski: Terapia fotodynamiczna jest wysoce efektywną metodą leczenia liszaja twardzinowego sromu.

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“…We hypothesize that chronic inflammation is an environment likely to induce fascin expression. There are several pieces of evidence that support this hypothesis: Fascin is overexpressed in inflammatory bowel disease and the expression correlates with the disease severity . Inflammation‐related cytokines TGF‐β and TNF‐α induce fascin expression .…”

Section: Discussionmentioning

confidence: 97%

Fascin regulates chronic inflammation‐related human colon carcinogenesis by inhibiting cell anoikis

et al. 2014

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By a proteomics-based approach, we identified an overexpression of fascin in colon adenocarcinoma cells (FPCKpP-3) that developed from nontumorigenic human colonic adenoma cells (FPCK-1-1) and were converted to tumorigenic by foreign-body-induced chronic inflammation in nude mice. Fascin overexpression was also observed in the tumors arising from rat intestinal epithelial cells (IEC 6) converted to tumorigenic in chronic inflammation which was induced in the same manner. Upregulation of fascin expression in FPCK-1-1 cells by transfection with sense fascin cDNA converted the cells tumorigenic, whereas antisense fascin-cDNA-transfected FPCKpP-3 cells reduced fascin expression and lost their tumor-forming ability in vivo. The tumorigenic potential by fascin expression was consistent with their ability to survive and grow in the three-dimensional multicellular spheroids. We found that resistance to anoikis (apoptotic cell death as a consequence of insufficient cell-to-substrate interactions), which is represented by the three-dimensional growth of solid tumors in vivo, was regulated by fascin expression through caspase-dependent apoptotic signals. From these, we demonstrate that fascin is a potent suppressor to caspase-associated anoikis and accelerator of the conversion of colonic adenoma cells into adenocarcinoma cells by chronic inflammation.

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The actin-bundling protein Fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair

Cited by 16 publications

References 25 publications

Rifaximin-Mediated Changes to the Epithelial Cell Proteome: 2-D Gel Analysis

Rifaximin-Mediated Changes to the Epithelial Cell Proteome: 2-D Gel Analysis

Efficacy of PDT in vulvar LS treatment based on immunohistochemical analysis of CD3, CD4, CD8, CD57, Granzyme B and Fascin expression

Fascin regulates chronic inflammation‐related human colon carcinogenesis by inhibiting cell anoikis

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