RT Journal Article
T1 Raloxifene and n-Acetylcysteine Ameliorate TGF-Signalling in Fibroblasts from Patients with Recessive Dominant Epidermolysis Bullosa
A1 Aguado Sánchez, Tania
A1 García, Marta
A1 García, Adela
A1 Ferrer-Mayorga, Gemma
A1 Martínez-Santamaría, Lucía
A1 Río, Marcela del
A1 Botella, Luisa-María
A1 Sánchez-Puelles, José-María
AB 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-β1, which is likely to be involved in the fibrosis that develops in this disease. Endoglin (CD105) is a type III coreceptor for TGF-β1 and its overexpression in fibroblasts deregulates physiological Smad/Alk1/Alk5 signalling, repressing the synthesis of TGF-β1 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.
PB MDPI
SN 2073-4409
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/91527
UL https://hdl.handle.net/20.500.14352/91527
LA eng
NO Aguado, T.; García, M.; García, A.; Ferrer-Mayorga, G.; Martínez-Santamaría, L.; del Río, M.; Botella, L.-M.; Sánchez-Puelles, J.-M. Raloxifene and n-Acetylcysteine Ameliorate TGF-Signalling in Fibroblasts from Patients with Recessive Dominant Epidermolysis Bullosa. Cells 2020, 9, 2108. https://doi.org/10.3390/cells9092108
NO Ministerio de Economía, Industria y Competitividad (España)
NO Comunidad de Madrid 
NO Centro de Investigación Biomédica en Red de Enfermedades Raras 
NO European Commission
DS Docta Complutense
RD 7 abr 2025