Late-onset renal hypertrophy and dysfunction in mice lacking CTRP1.

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.