Tao Liang, Chao Deng, Hang Guo, Zhenghao Dai, Yiwen Jiang, Yuting Lu, Weiguo Chen
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引用次数: 0
Abstract
This study aimed to investigate the therapeutic effects and underlying mechanisms of adipose-derived stem cell exosomes (ADSCs-exo) in ameliorating fibrosis in a rat model. ADSCs were isolated and cultured from rat adipose tissue, and ADSCs-exo were extracted via ultracentrifugation. Urethral fibrosis was induced by local injection of TGF-β1 (10 μg), followed by ADSCs-exo treatment. Urodynamic parameters were evaluated, and histological changes were evaluated using hematoxylin and eosin and Masson staining. Transcriptomic analysis and pathway enrichment were performed to identify signaling pathways regulated by ADSCs-exo. In vitro, urinary fibroblasts were stimulated with TGF-β1 and treated with ADSCs-exo alone or in combination with PDGF-BB (agonist) or imatinib (inhibitor). ADSCs-exo treatment significantly improved urodynamic function, reduced collagen deposition, and suppressed fibrosis-related protein expression in vivo. Transcriptomic analysis revealed platelet-derived growth factor and TGF-β pathways as major contributors to fibrosis. In vitro, ADSCs-exo significantly reduced TGF-β1-induced fibroblast proliferation, migration, and fibrosis-related protein expression, effects that were reversed by PDGF-BB and enhanced by imatinib. These findings were consistent in vivo, further supporting the hierarchical regulation of fibrosis-related signaling by ADSCs-exo. ADSCs-exo mitigates urethral stricture fibrosis by primarily suppressing the TGF-β/Smad pathway, thereby downregulating the downstream PDGFR-β/RAS/ERK axis, highlighting its therapeutic potential as a cell-free therapeutic approach for fibrotic urethral disease.
期刊介绍：
The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies.
Research manuscripts can be published under two different sections :
In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research.
In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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