Related Experiment Video
Updated: Dec 31, 2025
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Late-onset renal hypertrophy and dysfunction in mice lacking CTRP1
Susana Rodriguez1,2, Hannah C Little1,2, Parnaz Daneshpajouhnejad3
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract:
Local and systemic factors that influence renal structure and function in aging are not well understood. The secretory protein C1q/TNF-related protein 1 (CTRP1) regulates systemic metabolism and cardiovascular function. We provide evidence here that CTRP1 also modulates renal physiology in an age- and sex-dependent manner. In mice lacking CTRP1, we observed significantly increased kidney weight and glomerular hypertrophy in aged male but not female or young mice. Although glomerular filtration rate, plasma renin and aldosterone levels, and renal response to water restriction did not differ between genotypes, CTRP1-deficient male mice had elevated blood pressure. Echocardiogram and pulse wave velocity measurements indicated normal heart function and vascular stiffness in CTRP1-deficient animals, and increased blood pressure was not due to greater salt retention. Paradoxically, CTRP1-deficient mice had elevated urinary sodium and potassium excretion, partially resulting from reduced expression of genes involved in renal sodium and potassium reabsorption. Despite renal hypertrophy, markers of inflammation, fibrosis, and oxidative stress were reduced in CTRP1-deficient mice. RNA sequencing revealed alterations and enrichments of genes in metabolic processes in CTRP1-deficient animals. These results highlight novel contributions of CTRP1 to aging-associated changes in renal physiology.
Insights
The secretory protein CTRP1 influences kidney health in aging. CTRP1 deficiency increased kidney size and blood pressure in older male mice, revealing its role in age-related renal changes.
Area of Science:
- Nephrology
- Endocrinology
- Gerontology
Background:
- Aging impacts renal structure and function through poorly understood local and systemic factors.
- The secretory protein C1q/TNF-related protein 1 (CTRP1) is known to regulate systemic metabolism and cardiovascular function.
Purpose of the Study:
- To investigate the role of CTRP1 in modulating renal physiology in an age- and sex-dependent manner.
- To elucidate the mechanisms underlying CTRP1's influence on kidney function during aging.
Main Methods:
- Utilized CTRP1-deficient mice to assess age- and sex-specific renal phenotypes.
- Measured kidney weight, glomerular hypertrophy, glomerular filtration rate, plasma renin and aldosterone, blood pressure, echocardiogram, pulse wave velocity, and urinary electrolyte excretion.
- Performed RNA sequencing to analyze gene expression alterations in CTRP1-deficient kidneys.
Main Results:
- CTRP1 deficiency led to increased kidney weight and glomerular hypertrophy in aged male mice, but not females or young mice.
- CTRP1-deficient male mice exhibited elevated blood pressure without changes in heart function, vascular stiffness, or salt retention.
- Paradoxically, CTRP1 deficiency resulted in increased urinary sodium and potassium excretion, linked to reduced expression of reabsorption genes, and decreased renal inflammation, fibrosis, and oxidative stress.
Conclusions:
- CTRP1 plays a significant role in age- and sex-dependent regulation of renal physiology.
- CTRP1 deficiency impacts renal structure, blood pressure, and electrolyte handling in aging male mice.
- These findings highlight novel contributions of CTRP1 to aging-associated renal changes and suggest potential therapeutic targets.
