ArticleKidney international2012
Transcription factor FoxO1, the dominant mediator of muscle wasting in chronic kidney disease, is inhibited by microRNA-486.
Article in Kidney international, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 211 citations in OpenAlex.
- PI3K-AKT-FOXO1 pathway targeted by skeletal muscle microRNA to suppress proteolytic gene expression in response to carbohydrate intake during aerobic exercise.Physiological reports · 2018Trial
- Resistance Exercise Training Selectively Modulates Tumor Suppressor and Muscle-Regulatory MicroRNAs in Breast Cancer Survivors and Healthy Postmenopausal Women: An Exploratory Study.International journal of molecular sciences · 2026Article
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- Brain senescence drives sarcopenia-like transcriptomic remodeling in skeletal muscle.GeroScience · 2026Article
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Chronic Resistance Exercise Combined with Nutrient Timing Enhances Skeletal Muscle Mass and Strength While Modulating Small Extracellular Vesicle miRNA Profiles.Biomedicines · 2026Article
- Chronic Kidney Disease, Sarcopenia, and Hormonal-Metabolic Alterations: An Intriguing Association.Kidney & blood pressure research · 2026Review
- PHLDA1 is a shared diagnostic and key mediator of inflammatory fibrosis in heart and kidney.Frontiers in immunology · 2026Article
- The Impact of Exercise Capacity on Complex Neuromuscular Adaptations: A Narrative Review Based on a Rat Model System Selectively Bred for Low and High Response to Training.Comprehensive Physiology · 2025Review
- miR-486-5p Inhibits eNOS and Angiogenesis in Cultured Endothelial Cells by Targeting MAML3.Journal of cellular and molecular medicine · 2025Article
- Renin angiotensin system-induced muscle wasting: putative mechanisms and implications for clinicians.Molecular and cellular biochemistry · 2025Review
- Inhibiting Myostatin Expression by the Antisense Oligonucleotides Improves Muscle Wasting in a Chronic Kidney Disease Mouse Model.International journal of molecular sciences · 2025Article
- Sarcopenia in Chronic Kidney Disease: A Narrative Review from Pathophysiology to Therapeutic Approaches.Biomedicines · 2025Review
- Alteration of chromatin states perturb the transcription regulation of gene during hydronephrosis.Frontiers in genetics · 2025Article
- RNA signaling in skeletal muscle: the central role of microRNAs and exosomal microRNAs.Frontiers in cell and developmental biology · 2025Review
- Neuroprotective macromolecular methylprednisolone prodrug nanomedicine prevents glucocorticoid-induced muscle atrophy and osteoporosis in a rat model of spinal cord injury.Nanomedicine : nanotechnology, biology, and medicine · 2024Article
- Muscle-enriched microRNA-486-mediated regulation of muscular atrophy and exercise.Journal of physiology and biochemistry · 2024Review
- Synergistic Effects of Korean Mistletoe and Apple Peel Extracts on Muscle Strength and Endurance.Nutrients · 2024Article
- Functional Role of Extracellular Vesicles in Skeletal Muscle Physiology and Sarcopenia: The Importance of Physical Exercise and Nutrition.Nutrients · 2024Review
- The Rubicon-WIPI axis regulates exosome biogenesis during ageing.Nature cell biology · 2024Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic kidney disease (CKD) accelerates muscle protein degradation by stimulating the ubiquitin proteasome system through activation of the E3 ligases, Atrogin-1/MAFbx and MuRF-1. Forkhead transcription factors (FoxOs) can control the expression of these E3 ligases, but the contribution of individual FoxOs to muscle wasting is unclear. To study this we created mice with a muscle-specific FoxO1 deletion. The absence of FoxO1 blocked 70% of the increase in E3 ligase induction by CKD as well as the proteolysis and loss of muscle mass. Thus, FoxO1 has a role in controlling ubiquitin proteasome system-related proteolysis. As microRNA (miR)-486 reportedly dampens FoxO1 expression and its activity,we transfected a miR-486 mimic into primary cultures of myotubes and found this blocked dexamethasone-stimulated protein degradation without influencing protein synthesis.It also decreased FoxO1 protein translation and increased FoxO1 phosphorylation by downregulation of PTEN phosphatase, a negative regulator of p-Akt. To test its efficacy in vivo, we electroporated miR-486 into muscles and found that the expression of the E3 ligases was suppressed and muscle mass increased despite CKD. Thus, FoxO1 is a dominant mediator of CKD-induced muscle wasting, and miR-486 coordinately decreases FoxO1 and PTEN to protect against this catabolic response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.