#915 Role of VSIG4 in renal aging process

Abstract

Abstract Background and Aims V-set Ig domain-containing 4 (VSIG4), known for its role in inflammation and fibrosis, is particularly interesting in the realm of chronic kidney diseases. However, its specific role in kidney aging, especially under the influence of diabetes, is not well understood. This study aims to elucidate the role of VSIG4 in the aging process of kidneys, particularly in the diabetes. Method This study used male db/db and db/m mice, beginning from the age of eight weeks and spanning 38 weeks. Urinary albumin and VSIG4 levels were assessed using 6-hour timed urine collections and ELISA. The intrarenal expression of VSIG4 and klotho were analyzed through qRT-PCR and Western blotting. Results Urinary albumin levels in db/db mice were significantly higher from 8 weeks onward compared to db/m mice. These levels increased progressively with age, peaking at 38 weeks. Similarly, urinary VSIG4 levels showed a significant initial increase in db/db mice, followed by a consistent rise with age. Interestingly, both urinary albumin and VSIG4 levels in db/m mice showed a sudden surge at 38 weeks. Notably, urinary VSIG4 levels paralleled these changes in albumin levels, with a correlation coefficient of 0.867 (p < 0.001). Intrarenal VSIG4 mRNA expression was markedly higher in diabetic mice and showed a significant increase at 16 and 38 weeks, with the 38-week levels being fivefold higher in db/m mice. The expression trends of VSIG4 protein were similar to its mRNA expression. The study also monitored intrarenal klotho expression to assess aging, which revealed a progressive decrease in both mRNA and protein levels with age. Conclusion This study highlights a significant upregulation of both urinary and intrarenal VSIG4 expressions in diabetic and non-diabetic mice. The strong association of urinary VSIG4 expression with albuminuria suggests its involvement in the renal aging process, potentially contributing to the pathogenesis of age-related kidney alterations.