ArticleIn vivo (Athens, Greece)
Combined All-trans Retinoic Acid and Rosiglitazone Alleviates Scleroderma Fibrosis by Suppressing the STAT3/Th17 Axis.
Article in In vivo (Athens, Greece). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND/
aimEffective disease-modifying therapies for systemic sclerosis (scleroderma) remain a major clinical challenge. While all-trans retinoic acid (ATRA) and the PPARγ agonist rosiglitazone (RGZ) possess individual anti-fibrotic properties, their combined therapeutic potential and underlying mechanisms in scleroderma are unexplored. MATERIALS AND
methodsThis study investigated the efficacy and mechanisms of combined ATRA and RGZ therapy in a bleomycin (BLM)-induced murine scleroderma model and TGF-β1-stimulated NIH-3T3 fibroblasts. Pathological changes were assessed
resultsBLM-challenged mice exhibited pronounced dermal thickening, excessive collagen accumulation, and elevated Th17-related inflammatory responses. Strikingly, the ATRA+RGZ combination therapy significantly outperformed either monotherapy, robustly restoring normal skin architecture, reducing collagen density, and suppressing the expression of fibrotic mediators (TGF-β1, COL1a1) and Th17-associated factors (IL-17A, IL-6).
conclusionThe concurrent administration of ATRA and RGZ exerts superior protection against scleroderma fibrosis by converging on the inhibition of the STAT3/Th17 signaling axis. This study provides a compelling mechanistic rationale for repurposing and combining ATRA and RGZ as a translational strategy for scleroderma treatment.
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