The role and mechanism of protein synthesis in muscle atrophy induced by acute kidney injury
10.19405/j.cnki.issn1000–1492.2026.03.005
- VernacularTitle:蛋白质合成在急性肾损伤诱发肌肉萎缩中的作用与机制研究
- Author:
Xiaolin LIU
1
;
Qiongzhi ZHAO
1
;
Bin GUO
1
;
Sheng ZHANG
1
Author Information
1. Department of Cell Biology， School of Basic Medical Sciences， Southern Medical University， Guangzhou 510515
- Publication Type:Journal Article
- Keywords:
skeletal muscle atrophy;
acute kidney injury;
ribosomal biosynthesis;
protein synthesis;
rDNA transcription
- From:
Acta Universitatis Medicinalis Anhui
2026;61(3):416-423
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the role and mechanism of ribosomal DNA （rDNA） transcription and ribosome biogenesis in muscle atrophy induced by acute kidney injury （AKI）. MethodsEight male C57BL/6 mice were randomly divided into a control group （Ctrl） and a model group （AKI）. An AKI model was established via intraperitoneal injection of cisplatin. Muscle atrophy was phenotypically assessed by measuring muscle mass， myofiber cross-sectional area （HE staining）， and mRNA expression levels of atrophy-related genes （Murf-1， Atrogin-1， Igf-1） using qRT-PCR. In vivo protein synthesis rates were determined via the SUnSET assay （puromycin incorporation）. Ribosome biogenesis was evaluated by assessing rRNA content and 47S pre-rRNA expression levels. Myotubes differentiated from mouse skeletal muscle cell lines （C2C12 myotubes） were treated with serum from AKI mice， and the effects on rDNA transcription， ribosome biogenesis， and protein metabolism were analyzed using chromatin immunoprecipitation followed by quantitative polymerase chain reaction （ChIP-qPCR） and Western blot. ResultsAKI successfully induced muscle atrophy， as evidenced by a significant reduction in skeletal muscle mass. The most pronounced decrease occurred in the extensor digitorum longus muscle （21.0%， P 0.01）， along with a trend toward reduced myofiber cross-sectional area. At the molecular level， AKI inhibited muscle protein synthesis （83.14% reduction in puromycin incorporation， P 0.000 1） and impaired ribosome biogenesis， manifested by suppressed rDNA transcription elongation （52.62% decrease in 47S pre-rRNA ITS-1 levels， P 0.01） and reduced total rRNA content （65.29%， P 0.000 1）. In contrast， serum from AKI mice promoted rDNA transcription initiation and protein synthesis in C2C12 myotubes in vitro. ConclusionAKI induces muscle atrophy by suppressing rDNA transcription and ribosome biogenesis in skeletal muscle， leading to impaired protein synthesis. Dysregulated ribosome biogenesis may play a critical role in AKI-induced muscle atrophy.
