VSIG4 Expression During Renal Aging Is Accelerated by Type 2 Diabetes in Mice

A V-set Ig domain-containing 4 (VSIG4), known for complement receptor, has been involved in the profibrotic pathway in chronic kidney disease including diabetic kidney disease. However, its relationship with renal aging has not been examined longitudinally. This study aims to elucidate the role of VSIG4 in the aging process of kidneys, particularly in diabetes. Male db/m and db/db mice were followed from 8 to 38 weeks. Urinary albumin and VSIG4 levels were assessed using 6 h timed urine collections and ELISA. The intrarenal expression of VSIG4 and klotho were analyzed through immunohistochemical stating. In db/db mice, urinary albumin levels 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. Urinary VSIG4 levels showed a strong correlation with urinary albumin levels (r = 0.867, p < 0.001). Intrarenal VSIG4 expression increased with age, appearing earlier and more predominantly in diabetic mice, and was predominantly localized to distal tubular segments, while klotho expression progressively declined. These findings indicate that VSIG4 expression changes with renal aging and that diabetes is associated with earlier activation of this process. Urinary VSIG4 reflects aging-related kidney changes rather than diabetic injury alone.