Targeting endothelial-to-mesenchymal transition: the protective role of hydroxytyrosol sulfate metabolite.
Purpose: Endothelial-to-mesenchymal transition (EndMT) plays an important role in pathogenesis of a number of inflammatory diseases. Hydroxytyrosol (HT) and, particularly, its major plasma metabolite HT-3O sulfate (HT-3Os) are known olive oil antioxidant and anti-inflammatory polyphenols which exert...
| Publicado en: | European Journal of Nutrition Vol. 59; no. 2; pp. 517 - 528 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Mar2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142084293&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142084293 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14366207 CR0 jtl: European Journal of Nutrition issn: 14366207 maglogo: N pubinfo: dt: Mar2020 vid: 59 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 142084293 142084293 142084293 10.1007/s00394-019-01920-x 142084293 ppf: 517 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Targeting endothelial-to-mesenchymal transition: the protective role of hydroxytyrosol sulfate metabolite. aug: au: Terzuoli, Erika Nannelli, Ginevra Giachetti, Antonio Morbidelli, Lucia Ziche, Marina Donnini, Sandra affil: Department of Life Sciences, University of Siena, Siena, Italy sug: subj: Epithelial Cells Drug Effects Cell Physiology Drug Effects Olive Oil Pharmacodynamics Polyphenols Pharmacodynamics Antiinflammatory Agents Pharmacodynamics Metabolites Inflammation Drug Therapy Human In Vitro Studies Transforming Growth Factor beta Drug Effects Receptors, Cell Surface Drug Effects Interleukins Vascular Diseases Drug Therapy Retinal Diseases Drug Therapy Gene Expression Drug Effects Transcription Factors Drug Effects Signal Transduction Drug Effects Animal Studies Phenotype Drug Effects Genetic Markers Drug Effects Matrix Metalloproteinases Drug Effects MicroRNA Drug Effects ab: Purpose: Endothelial-to-mesenchymal transition (EndMT) plays an important role in pathogenesis of a number of inflammatory diseases. Hydroxytyrosol (HT) and, particularly, its major plasma metabolite HT-3O sulfate (HT-3Os) are known olive oil antioxidant and anti-inflammatory polyphenols which exert benefits against vascular diseases by improving endothelial function. However, to date the HT-3Os role in EndMT is not well known. Methods: To investigate the HT-3Os effects on EndMT in the inflamed endothelium, we used an in vitro model of endothelial dysfunction, challenging endothelial cells (EC), human umbilical EC (HUVEC) and human retinal EC (HREC) with Interleukin-1β (IL-1β), an inflammatory agent. HREC were used as a specific model to investigate HT-3Os effects on vascular retinal diseases. Results: We found that IL-1β treatment-induced EndMT phenotype in both cell models, also changing cell morphology. HT-3Os protected EC against IL-1β effects, recovering cell morphology and phenotype. Mechanistically, HT-3Os targeting fibroblast growth factor receptor 1 FGFR1 expression and let-7 miRNA, controlled transforming growth factor beta (TGF-β) signalling in EC, downregulating transcription factors expression (SNAI1 and ZEB2) and gene expression of late EndMT markers (FN1, VIM, NOTCH3, CNN1, MMP2 and MMP9). Conclusion: These results demonstrate that HT-3Os blunts pathological EndMT in inflamed EC, maintaining high let-7 miRNA expression and preventing activation of TGF-β signalling. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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