Late-onset renal hypertrophy and dysfunction in mice lacking CTRP1.
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.
['Rodriguez|Susana|S|', 'Little|Hannah C|HC|', 'Daneshpajouhnejad|Parnaz|P|', 'Shepard|Blythe D|BD|', 'Tan|Stefanie Y|SY|', 'Wolfe|Andrew|A|', 'Cheema|Muhammad Umar|MU|', 'Jandu|Sandeep|S|', 'Woodward|Owen M|OM|', 'Talbot|C Conover|CC|', 'Berkowitz|Dan E|DE|', 'Rosenberg|Avi Z|AZ|', 'Pluznick|Jennifer L|JL|', 'Wong|G William|GW|']
D054392:Adipokines D000818:Animals D001794:Blood Pressure D006973:Hypertension D006984:Hypertrophy D007249:Inflammation D007668:Kidney D018345:Mice, Knockout D015398:Signal Transduction
C1q/TNF-related protein 1 aging-associated renal physiology kidney function