谷歌浏览器插件
订阅小程序
在清言上使用

Indoxyl Sulfate Inhibits Muscle Cell Differentiation Via Myf6/MRF4 and MYH2 Downregulation

NEPHROLOGY DIALYSIS TRANSPLANTATION(2023)

引用 0|浏览30
暂无评分
摘要
BACKGROUND Chronic kidney disease is associated with a significant decrease in muscle strength and mass, possibly related to muscle cell damage by uremic toxins. Here, we studied in vitro and in vivo the effect of indoxyl sulfate (IS), an indolic uremic toxin, on myoblast proliferation, differentiation, expression of myogenic regulatory factors (MRF): myoblast determination protein 1 (MyoD1), myogenin (Myog), Myogenic Factor 5 (Myf5), and myogenic regulatory factor 4 (Myf6 /MRF4), and expression of myosin heavy chain, Myh2. METHODS C2C12 myoblasts were cultured in vitro and differentiated in myotubes for 7 days in presence of IS at a uremic concentration of 200 µM. Myocytes morphology and differentiation was analyzed after Hematoxylin-eosin staining. MRF genes expression was studied using RT-PCR in myocytes and 5/6th nephrectomized mice muscle. Myf6 /MRF4 protein expression was studied using ELISA; MYH2 protein expression was studied using western blotting. The role of Aryl Hydrocarbon Receptor (AHR) - the cell receptor of IS- was studied by adding an AHR inhibitor in cell culture milieu. RESULTS In presence of IS, myotubes obtained were narrower and had less nuclei than control myotubes. The presence of IS during differentiation did not modify the gene expression of the MRFs Myf5, MyoD1, and Myog, but induced a decrease in expression of Myf6/MRF4 and MYH2 at the mRNA and the protein level. AHR inhibition by CH223191 did not reverse the decrease in Myf6/MRF4 mRNA expression induced by IS, which rules out the implication of the ARH genomic pathway. In 5/6th nephrectomized mice, Myf6/MRF4 gene was down-regulated in striated muscles. CONCLUSION In conclusion, IS inhibits Myf6/MRF4 and MYH2 expression during differentiation of muscle cells, which could lead to a defect in myotube structure. Through these new mechanisms, IS could participate in muscle atrophy observed in chronic kidney disease.
更多
查看译文
关键词
chronic kidney disease,indoxyl sulfate,myogenesis,uremic toxin
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要