Reduced LRP6 expression and increase in the interaction of GSK3β with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea

The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial

“…It is also possible that inhibition of inflammatory mediators (such as TNF-α) may have contributed to the beneficial effect of GTP17. The findings of the current study confirm in a clinical setting our preclinical study that suggested the ability of green tea to reduce albuminuria in diabetic nephropathy, probably by diminishing podocyte apoptosis through activation of the WNT pathway12.…”

“…On the contrary, Kato and colleagues have suggested that down-regulation of the WNT pathway in podocytes might in fact enhance apoptosis susceptibility14. This last suggestion was confirmed by our recent observations, wherein we demonstrated—both in vivo and in vitro —that high glucose or blockage of the WNT receptor, LRP6, with DKK-1 or silencing RNA increases glycogen synthase kinase 3 beta (GSK3β), its interaction with p53, and ultimately podocyte apoptosis12. GSK3β is involved in WNT pathway regulation22.…”

“…Preclinical studies in diabetic nephropathy101112 and in rapidly progressive glomerulonephritis13 have demonstrated that green tea (GT) is able to reduce albuminuria and other markers of renal damage. In experimental DN studies, GT was able to reduce oxidative stress markers by inhibiting NOX4, as well as nitric oxidase synthase (NOS) uncoupling1011.…”

“…In experimental DN studies, GT was able to reduce oxidative stress markers by inhibiting NOX4, as well as nitric oxidase synthase (NOS) uncoupling1011. In addition, we recently demonstrated that under experimental diabetic conditions, GT reduces podocyte apoptosis by activating the WNT pathway12. Interestingly, GT was not able to reduce podocyte apoptosis when podocytes exposed to high glucose were treated with dickkopf 1 (DKK-1).…”

“…DKK-1 is a blocker of low-density lipoprotein receptor-related protein 6 (LRP6), a receptor of the WNT pathway that is involved in podocyte death under conditions of high glucose exposure14. We concluded that GT could ameliorate albuminuria by reducing podocyte apoptosis through activation of the WNT pathway12.…”