Multiomics Analysis Reveals Therapeutic Targets for Chronic Kidney Disease With Sarcopenia

作者：Meiqiu Wang, Lianghui You, Xu He, Yingchao Peng, Ren Wang, Zhiqiang Zhang, Jiaping Shu, Pei Zhang, Xiaoyi Sun, Lili Jia, Zhengkun Xia, Chenbo Ji, Chunlin Gao · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2025 · DOI：10.1002/jcsm.13696 · 被引用次数：11 · 研究领域：Muscle Physiology and Disorders、Nutrition and Health in Aging、Cardiomyopathy and Myosin Studies

BACKGROUND: The presence of sarcopenia in patients with chronic kidney disease (CKD) is associated with poor prognosis. The mechanism underlying CKD-induced muscle wasting has not yet been fully explored. This study investigates the influence of renal secretions on muscles using multiomics sequencing. METHODS: The kidney transcriptome analysis by RNA-seq and protein profiling by tandem mass tag (TMT), serum TMT and muscle TMT were performed in CKD established using 0.2% adenine and control mice. Spp1 recombinant protein was used to study its effect on myotube atrophy in vitro. In animal experiments on CKD, pharmacological inhibition of Spp1 was used to explore the role of Spp1 in skeletal muscle wasting. Transcriptome analysis was performed to identify differentially expressed genes (DEGs) in the gastrocnemius muscle following Spp1 pharmacological inhibition. RESULTS: In the renal transcriptome and TMT, 503 and 377 proteins/genes respectively were co-upregulated and co-downregulated. In the serum TMT of CKD and normal control (NC) mice, 22 upregulated and 7 downregulated differentially expressed proteins (DEPs) showed the same expression patterns as those in the kidney transcriptome and TMT analysis. Based on bioinformatics analysis and reported studies, we selected Spp1 for further validation. Spp1 recombinant protein was added to C2C12 myotubes in vitro, and the results indicated that Spp1 significantly increased the protein levels of the muscle atrophy marker (Murf-1) and ...