RETRACTED ARTICLE: Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells
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Dossier post-publication
- Nature
- Retraction
- Motif
- Duplication of/in Image;Euphemisms for Duplication;Unreliable Results and/or Conclusions;
- Date
- 9/29/2023 0:00
- Signalé par OpenAlex ?
- Oui
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Résumé
Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation of A2A receptor reduced the overexpression of the EMT-related markers, mainly through the cAMP-dependent PKA pathway, as confirmed by cell pre-treatment with Myr-PKI. Both A1 and P2Y1 receptor stimulation exacerbated the TGF-β1-driven effects, which were reduced by cell pre-treatment with the MAPK inhibitor PD98059, according to the increased ERK1/2 phosphorylation upon receptor activation. The effects induced by P2Y11 receptor activation were oppositely modulated by PKA or MAPK inhibition, in line with the dual nature of the Gs- and Gq-coupled receptor. Differently, P2X7 receptor induced, per se, similar and not additive effects compared to TGF-β1, after prolonged cell exposure to BzATP. These results suggest a putative role of purine receptors as target for anti-fibrotic agents.
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La notice
- Revue
- Purinergic Signalling
- Thématique
- Congenital Diaphragmatic Hernia Studies
- Domaine
- Medicine
- Établissements canadiens
- McMaster University
- Organismes subventionnaires
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Mots-clés
- Epithelial–mesenchymal transitionReceptorMAPK/ERK pathwayCell biologyCancer researchMesenchymal stem cellSignal transductionFibronectinBiologyChemistryDownregulation and upregulationBiochemistryExtracellular matrix
- Résumé présent dans OpenAlex
- oui