Work

APLNR reduction in kidney-muscle crosstalk in renal model recovered by exercise and STAT3 inhibition

Year: 2026

Type: article

Abstract: Current evidence show that exercise has beneficial effects on skeletal muscle function in individuals with chronic kidney disease (CKD). The STAT3 signaling pathway and the apelin axis (apelin receptor, APLNR- and ligands, -apelin and/or -elabela), participate in the processes of kidney inflammation and fibrosis and both may be involved in muscle wasting during CKD. Herein we report that STAT3 pathway and APLNR are in fact involved in the muscle impairment concomitant to CKD in experimental model and in adult individuals with CKD. Male BALB/c mice were first submitted to an 8-week ladder climbing resistance training (RT) protocol and further were submitted to doxorubicin-induced experimental CKD with or without use of the STAT3 inhibitor (Stattic). The GSE157712 dataset was used to assess the muscle transcriptome profile of CKD patients. Bioinformatics' analysis of gene set enrichment analysis (GSEA) and gene ontology (GO) were performed and the APLNR was found to be a central component of muscle response over kidney stress. Mice from the RT protocol showed a protective effect of blocking STAT3 against kidney and muscle injury markers, while both CKD individuals and CKD mice reported alterations in the APLNR muscle expression. In conclusion, the muscle tissue function is affected during CKD, which can be attenuated by a protective and synergistic effect of exercise and STAT3 inhibition. Thus, APLNR appears as a key gene associated with muscle dysfunction in CKD patients and its muscle expression can be regulated by resistance exercise.

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2026.102565