4.7 Article

Apparent Absence of BMAL1-Dependent Skeletal Muscle-Kidney Cross Talk in Mice

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BIOMOLECULES
卷 12, 期 2, 页码 -

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MDPI
DOI: 10.3390/biom12020261

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circadian clock genes; renal function; integrative physiology

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The study found that iMS-BMAL1 KO mice exhibited an aging phenotype with no renal phenotype, and their response to low potassium diet and phase advance in renal function was similar to the control group, indicating that disruption of the clock in skeletal muscle does not lead to significant renal injury.
BMAL1 is a core mammalian circadian clock transcription factor responsible for the regulation of the expression of thousands of genes. Previously, male skeletal-muscle-specific BMAL1-inducible-knockout (iMS-BMAL1 KO) mice have been described as a model that exhibits an aging-like phenotype with an altered gait, reduced mobility, muscle weakness, and impaired glucose uptake. Given this aging phenotype and that chronic kidney disease is a disease of aging, the goal of this study was to determine if iMS-BMAL1 KO mice exhibit a renal phenotype. Male iMS-BMAL1 KO and control mice were challenged with a low potassium diet for five days. Both genotypes responded appropriately by conserving urinary potassium. The iMS-BMAL1 KO mice excreted less potassium during the rest phase during the normal diet but there was no genotype difference during the active phase. Next, iMS-BMAL1 KO and control mice were used to compare markers of kidney injury and assess renal function before and after a phase advance protocol. Following phase advance, no differences were detected in renal mitochondrial function in iMS-BMAL1 KO mice compared to control mice. Additionally, the glomerular filtration rate and renal morphology were similar between groups in response to phase advance. Disruption of the clock in skeletal muscle tissue activates inflammatory pathways within the kidney of male mice, and there is evidence of this affecting other organs, such as the lungs. However, there were no signs of renal injury or altered function following clock disruption of skeletal muscle under the conditions tested.

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