Raloxifene and n-Acetylcysteine ameliorate TGF-signalling in fibroblasts from patients with recessive dominant epidermolysis bullosa

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dc.contributor.author Aguado, Tania
dc.contributor.author García Díez, Marta
dc.contributor.author García Martín, Adela María
dc.contributor.author Ferrer-Mayorga, Gemma
dc.contributor.author Martínez Santamaría, Lucia
dc.contributor.author Río Nechaevsky, Marcela del
dc.contributor.author Botella Cubells, Luisa Maria
dc.contributor.author Sanchez-Puelles Gonzalez-Carvajal, Jose Maria
dc.date.accessioned 2022-06-30T15:18:48Z
dc.date.available 2022-06-30T15:18:48Z
dc.date.issued 2020-09-16
dc.identifier.bibliographicCitation Aguado, T., García, M., García, A., Ferrer-Mayorga, G., Martínez-Santamaría, L., del Río, M., Botella, L.-M., & Sánchez-Puelles, J.-M. (2020). Raloxifene and n-Acetylcysteine Ameliorate TGF-Signalling in Fibroblasts from Patients with Recessive Dominant Epidermolysis Bullosa. Cells, 9 (9), p. 2108.
dc.identifier.issn 2073-4409
dc.identifier.uri http://hdl.handle.net/10016/35363
dc.description.abstract Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disease caused by mutation of the COL7A1 gene. RDEB is associated with high levels of TGF-beta1, which is likely to be involved in the fibrosis that develops in this disease. Endoglin (CD105) is a type III coreceptor for TGF-beta1 and its overexpression in fibroblasts deregulates physiological Smad/Alk1/Alk5 signalling, repressing the synthesis of TGF-beta1 and extracellular matrix (ECM) proteins. Raloxifene is a specific estrogen receptor modulator designated as an orphan drug for hereditary hemorrhagic telangiectasia, a rare vascular disease. Raloxifene stimulates endoglin synthesis, which could attenuate fibrosis. By contrast, the antioxidant N-acetylcysteine may have therapeutic value to rectify inflammation, fibrosis and endothelial dysfunction. Thus, we present here a repurposing strategy based on the molecular and functional screening of fibroblasts from RDEB patients with these drugs, leading us to propose the repositioning of these two well-known drugs currently in clinical use, raloxifene and N-acetylcysteine, to counteract fibrosis and inflammation in RDEB. Both compounds modulate the profibrotic events that may ultimately be responsible for the clinical manifestations in RDEB, suggesting that these findings may also be relevant for other diseases in which fibrosis is an important pathophysiological event.
dc.description.sponsorship This work was supported by grants CTQ2014-52213-R, CTQ2015-64402-C2-1-R and CTQ2015-64402-C2-2-R (Spanish Ministry of Economy and Competitiveness, MINECO), CM S2011/BMED-2353 (Comunidad de Madrid), and FEDER Funds and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (ISCIII).
dc.language.iso eng
dc.publisher MDPI
dc.rights © The authors
dc.rights Atribución 3.0 España
dc.rights.uri http://creativecommons.org/licenses/by/3.0/es/
dc.subject.other Epidermolysis bullosa
dc.subject.other TGF-fibrosis
dc.subject.other Raloxifene
dc.subject.other N-acetylcysteine
dc.subject.other Endoglin
dc.subject.other Smad
dc.subject.other ALK1/5
dc.subject.other Drug repurposing
dc.title Raloxifene and n-Acetylcysteine ameliorate TGF-signalling in fibroblasts from patients with recessive dominant epidermolysis bullosa
dc.type article
dc.identifier.doi https://doi.org/10.3390/cells9092108
dc.rights.accessRights openAccess
dc.relation.projectID Gobierno de España. CTQ2014-52213-R
dc.relation.projectID Gobierno de España. CTQ2015-64402-C2-1-R
dc.relation.projectID Gobierno de España. CTQ2015-64402-C2-2-R
dc.relation.projectID Comunidad de Madrid. CM S2011/BMED-2353
dc.type.version publishedVersion
dc.identifier.publicationfirstpage 1
dc.identifier.publicationissue 9
dc.identifier.publicationlastpage 18
dc.identifier.publicationtitle Cells
dc.identifier.publicationvolume 9
dc.identifier.uxxi AR/0000027447
dc.contributor.funder Ministerio de Economía y Competitividad (España)
dc.contributor.funder Comunidad de Madrid
dc.affiliation.dpto UC3M. Departamento de Bioingeniería
dc.affiliation.grupoinv UC3M. Grupo de Investigación: Tissue Engineering and Regenerative Medicine (TERMeG)
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