Abstract | OBJECTIVES: METHODS: RESULT:
Riociguat dose-dependently reduced skin thickening, myofibroblast differentiation and accumulation of collagen with potent antifibrotic effects at 1 and 3 mg/kg. Riociguat also ameliorated fibrosis of the gastrointestinal tract in the cGvHD model. The antifibrotic effects were associated with reduced phosphorylation of extracellular signal-regulated kinases. Sildenafil at doses of 3 and 10 mg/kg exerted mild antifibrotic effects that were significantly less pronounced compared with 1 and 3 mg/kg riociguat. CONCLUSIONS: These data demonstrated potent antifibrotic effects of riociguat on experimental skin and organ fibrosis. These findings suggest a role for riociguat for the treatment of fibrotic diseases, especially for the treatment of SSc. A phase II study with riociguat in patients with SSc is currently starting.
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Authors | Clara Dees, Christian Beyer, Alfiya Distler, Alina Soare, Yun Zhang, Katrin Palumbo-Zerr, Oliver Distler, Georg Schett, Peter Sandner, Jörg H W Distler |
Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 74
Issue 8
Pg. 1621-5
(Aug 2015)
ISSN: 1468-2060 [Electronic] England |
PMID | 25817717
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. |
Chemical References |
- Phosphodiesterase 5 Inhibitors
- Pyrazoles
- Pyrimidines
- Sildenafil Citrate
- Guanylate Cyclase
- riociguat
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Topics |
- Animals
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Fibrosis
- Guanylate Cyclase
(drug effects)
- Mice
- Mice, Inbred Strains
- Phosphodiesterase 5 Inhibitors
(pharmacology)
- Pyrazoles
(administration & dosage, pharmacology, therapeutic use)
- Pyrimidines
(administration & dosage, pharmacology, therapeutic use)
- Scleroderma, Systemic
(drug therapy)
- Sildenafil Citrate
(pharmacology)
- Skin
(pathology)
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