PROTECTIVE EFFECTS OF ISOLATED SOY PROTEINFEEDING ON RENAL TUBULES IN THE EARLY STAGEOF DIABETIC NEPHROPATHY.

Abstract

Progression of diabetic nephropathy (DN) is strongly related to the severity of tubulointerstitial damage. Isolated soy protein (ISP) feeding has shown beneficial effects in animal DN models. However, the mechanisms underlying the renal effects of ISP feeding in early disease stages have not been clarified. In this study, 6-week-old obese Zucker (fa/fa) rats and lean control rats were fed 20% casein or 20% ISP diet for either 2 or 24 weeks. In casein-fed fa/fa rats, the levels of urinary markers of tubular injury started to increase 2 weeks after the commencement of experimental feeding, and the increase continued over time. The levels of these markers were significantly lower in ISP-fed fa/fa rats than in casein-fed fa/fa rats. Renal MCP-1, IL-1β, and TNF- α mRNA levels and urinary MCP-1 levels were also lower in ISP-fed fa/fa rats than in casein-fed fa/fa rats after 2 weeks. IL- 1β-induced upregulation of MCP-1 expression in cultured tubular NRK-52E cells was suppressed by ISP peptides produced by digestion with pepsin and trypsin, but not by casein peptides. In conclusion, casein feeding induces tubular damage at the early stage of DN, whereas ISP feeding alleviates it. The renoprotective effects of ISP may be associated with the downregulation of renal inflammatory cytokines.