Endothelin 1 contributes to the effect of transforming growth factor beta1 on wound repair and skin fibrosis

Arthritis and Rheumatism
David LagaresFernando Rodríguez-Pascual

Abstract

To characterize the pathways induced by transforming growth factor beta1 (TGFbeta1) that lead to the expression of endothelin 1 (ET-1) in human dermal fibroblasts, and to study the effects of TGFbeta1 and ET-1 on the acquisition of a profibrotic phenotype and assess the contribution of the TGFbeta1/ET-1 axis to skin wound healing and fibrosis in vivo. The mechanism of induction of ET-1 expression by TGFbeta1 and its effect on the expression of alpha-smooth muscle actin and type I collagen were studied in human dermal fibroblasts, in experiments involving the TGFbeta receptor inhibitor GW788388 and the ET receptor antagonist bosentan, by real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, immunofluorescence, Western blotting, and promoter/reporter transient transfection analyses. Experiments assessing dermal wound healing in mice were performed with adenovirus-driven overexpression of active TGFbeta1 and ET-1, with or without treatment with bosentan. The contributions of TGFbeta1 and ET-1 to the fibrotic response were also assessed in a mouse model of bleomycin-induced skin fibrosis, by histologic, immunohistochemical, RT-PCR, and protein analyses. TGFbeta1 induced ET-1 expressi...Continue Reading

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Citations

Jan 18, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Paula B DonateFernando Q Cunha
Jan 19, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·David Lagares, Mohit Kapoor
Sep 11, 2012·American Journal of Respiratory Cell and Molecular Biology·David LagaresFernando Rodríguez-Pascual
Jan 28, 2012·Free Radical Biology & Medicine·Rosa Bretón-RomeroSantiago Lamas
Apr 12, 2012·Arthritis and Rheumatism·David LagaresFernando Rodríguez-Pascual
Aug 19, 2011·The British Journal of Dermatology·T TaniguchiS Sato
May 23, 2016·Arthritis Research & Therapy·Kengo AkashiAkio Morinobu
Jan 1, 2014·Life Sciences·Fernando Rodríguez-PascualJosé González-Santamaría
Dec 15, 2017·Science Translational Medicine·David LagaresAndrew M Tager
Jul 12, 2014·Journal of the American Society of Nephrology : JASN·Oscar BusnadiegoFernando Rodríguez-Pascual
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Jul 29, 2010·Journal of Dermatological Science·Yoshihide AsanoMaria Trojanowska

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