OBJECTIVES: There is increasing evidence that the endocannabinoid system may be involved in pathological fibrosis, and that its modulation might limit fibrotic responses. The aim of this study was to examine the capacity of a synthetic cannabinoid receptor agonist to modify skin fibrosis in the bleomycin mouse model of scleroderma. METHODS: Skin fibrosis was induced by local injections of bleomycin in two groups of DBA/2J mice. One group was cotreated with the synthetic cannabinoid WIN55,212-2 at 1 mg/kg/day. Skin fibrosis was evaluated by histology and skin thickness and hydroxyproline content were quantified. Markers of fibroblast activation, including α smooth muscle actin and the profibrotic cytokines transforming growth factor (TGF)β, connective tissue growth factor (CTGF) and platelet-derived growth factor (PDGF)-BB, were examined. Levels of PSMAD2/3, which are crucial in extracellular matrix overproduction, were analysed. RESULTS: Bleomycin treatment induced typical skin fibrosis. Upon WIN55,212-2 treatment dermal fibrosis was completely prevented. Subcutaneous inflammatory cell infiltration, dermal thickness and collagen content resulted similar to those of the control group. The synthetic cannabinoid prevented fibroblasts activation induced by bleomycin, paralleled by a strong inhibition of TGFβ, CTGF and PDGF-BB expression. Phosphorylation of SMAD2/3 was significantly downregulated after WIN55,212-2 exposure. CONCLUSIONS: Taken together, the results indicate that the synthetic cannabinoid WIN55,212-2 is capable of preventing skin fibrosis in a mouse model of scleroderma.
OBJECTIVES: There is increasing evidence that the endocannabinoid system may be involved in pathological fibrosis, and that its modulation might limit fibrotic responses. The aim of this study was to examine the capacity of a synthetic cannabinoid receptor agonist to modify skin fibrosis in the bleomycinmouse model of scleroderma. METHODS:Skin fibrosis was induced by local injections of bleomycin in two groups of DBA/2J mice. One group was cotreated with the synthetic cannabinoidWIN55,212-2 at 1 mg/kg/day. Skin fibrosis was evaluated by histology and skin thickness and hydroxyproline content were quantified. Markers of fibroblast activation, including α smooth muscle actin and the profibrotic cytokines transforming growth factor (TGF)β, connective tissue growth factor (CTGF) and platelet-derived growth factor (PDGF)-BB, were examined. Levels of PSMAD2/3, which are crucial in extracellular matrix overproduction, were analysed. RESULTS:Bleomycin treatment induced typical skin fibrosis. Upon WIN55,212-2 treatment dermal fibrosis was completely prevented. Subcutaneous inflammatory cell infiltration, dermal thickness and collagen content resulted similar to those of the control group. The synthetic cannabinoid prevented fibroblasts activation induced by bleomycin, paralleled by a strong inhibition of TGFβ, CTGF and PDGF-BB expression. Phosphorylation of SMAD2/3 was significantly downregulated after WIN55,212-2 exposure. CONCLUSIONS: Taken together, the results indicate that the synthetic cannabinoidWIN55,212-2 is capable of preventing skin fibrosis in a mouse model of scleroderma.
Authors: Debendra Pattanaik; Monica Brown; Bradley C Postlethwaite; Arnold E Postlethwaite Journal: Front Immunol Date: 2015-06-08 Impact factor: 7.561
Authors: Marisol Maya-López; Ana Laura Colín-González; Gabriela Aguilera; María Eduarda de Lima; Ana Colpo-Ceolin; Edgar Rangel-López; Juana Villeda-Hernández; Daniel Rembao-Bojórquez; Isaac Túnez; Armando Luna-López; Roberto Lazzarini-Lechuga; Viridiana Yazmín González-Puertos; Pedro Posadas-Rodríguez; Alejandro Silva-Palacios; Mina Königsberg; Abel Santamaría Journal: Am J Transl Res Date: 2017-02-15 Impact factor: 4.060
Authors: Irina Bronova; Brett Smith; Bulent Aydogan; Ralph R Weichselbaum; Kiran Vemuri; Katalin Erdelyi; Alex Makriyannis; Pal Pacher; Evgeny V Berdyshev Journal: Am J Respir Cell Mol Biol Date: 2015-10 Impact factor: 6.914
Authors: Marisol S Castaneto; David A Gorelick; Nathalie A Desrosiers; Rebecca L Hartman; Sandrine Pirard; Marilyn A Huestis Journal: Drug Alcohol Depend Date: 2014-08-18 Impact factor: 4.492
Authors: Carmen del Río; Carmen Navarrete; Juan A Collado; M Luz Bellido; María Gómez-Cañas; M Ruth Pazos; Javier Fernández-Ruiz; Federica Pollastro; Giovanni Appendino; Marco A Calzado; Irene Cantarero; Eduardo Muñoz Journal: Sci Rep Date: 2016-02-18 Impact factor: 4.379