Avtor/Urednik		Yamashita, Takashi; Lakota, Katja; Taniguchi, Takashi; Yoshizaki, Ayumi; Sato, Shinichi; Hong, Wen; Zhou, Xingchun; Sodin-Šemrl, Snežna; Fang, Feng; Yoshihide, Asano; Varga, John
Naslov		An orally-active adiponectin receptor agonist mitigates cutaneous fibrosis, inflammation and microvascular pathology in a murine model of systemic sclerosis
Tip		članek
Vol. in št.		Letnik 8, št. 1
Leto izdaje		2018
Obseg		str. 1-14
ISSN		2045-2322 - Scientific reports
Jezik		eng
Abstrakt		The hallmarks of systemic sclerosis (SSc) are autoimmunity, microangiopathy and fibrosis. Skin fibrosis is accompanied by attrition of the dermal white adipose tissue layer, and alterations in the levels and function of adiponectin. Since these findings potentially implicate adiponectin in the pathogenesis of SSc, we employed a novel pharmacological approach to augment adiponectin signaling using AdipoRon, an orally active adiponectin receptor agonist. Chronic treatment with AdipoRon significantly ameliorated bleomycin-induced dermal fibrosis in mice. AdipoRon attenuated fibroblast activation, adipocyte-to-myofibroblast transdifferentiation, Th2/Th17-skewed polarization of the immune response, vascular injury and endothelial-to-mesenchymal transition within the lesional skin. In vitro, AdipoRon abrogated profibrotic responses elicited by TGF-[beta] in normal fibroblasts, and reversed the inherently-activated profibrotic phenotype of SSc fibroblasts. In view of these broadly beneficial effects on all three cardinal pathomechanisms underlying the clinical manifestations of SSc, pharmacological augmentation of adiponectin signaling might represent a novel strategy for the treatment of SSc.
Proste vsebinske oznake		adiponectin systemic sclerosis inflammation and microvascular pathology adiponektin sistemska skleroza vnetje in mikrovaskularna patologija