Interplay between Skeletal Muscle Catabolism and Remodeling of Arteriovenous Fistula by Yes-Associated Protein 1 (YAP1) Signaling

作者：Yongdong Wu, Tae Hoon Lee, Owen H. Cheng, Eric K. Peden, Qingtian Li, Jun Wang, Fengzhang Huang, Marites P. Melancon, David Sheikh‐Hamad, Tao Wang, Luan D. Truong, William E. Mitch, Ming Liang, Jizhong Cheng · 发表于：Journal of the American Society of Nephrology · 年份：2025 · DOI：10.1681/asn.0000000605 · 被引用次数：3 · 研究领域：Tissue Engineering and Regenerative Medicine、Diagnosis and Treatment of Venous Diseases

Key Points Atrophied muscle–derived myostatin stimulated mesenchymal stem cell differentiation and adverse arteriovenous (AV) fistula remodeling through yes-associated protein 1 (YAP1) activation. Treatment with myostatin peptibody inhibited muscle wasting and blocked mesenchymal stem cell activation and AV fistula fibrosis. A light-sensitive drug-release strategy was engineered for the periadventitial delivery of verteporfin to improve AV fistula patency. Background Arteriovenous (AV) fistulas are the preferred access for dialysis but have a high incidence of failure. The aim of this study was to understand the crosstalk between skeletal muscle catabolism and AV fistula maturation failure. Methods Skeletal muscle metabolism and AV fistula maturation were evaluated in mice with CKD. The roles of myostatin and yes-associated protein 1 (YAP1) in regulating the transdifferentiation of adventitial mesenchymal stem cells (MSCs) and intima hyperplasia in AV fistula were investigated. Nanoparticles carrying a YAP1 inhibitor, verteporfin, with light irradiation–controlled release were synthesized and applied to AV fistula. Results Increased trichrome signals and stenosis were observed in AV fistulas from mice treated with myostatin and from mice with CKD. By contrast, blocking myostatin function with an anti-myostatin peptibody not only improved body weight and muscle size in CKD mice but also decreased neointima formation in AV fistulas. In cultured MSCs, myostatin induced YAP1 expr...