Fig. 3. Rapid accumulation of PHF1 tau in Il33^−/− brain after oxidative stress surge positively correlates to reduction of PHF1 tau in mesangial cells in their kidneys.

a Immunofluorescence shows more PHF1 (green) in glomeruli of WT mice than Il33^−/− littermates at 70 weeks; right panels are enlarged boxed areas of left panels to show PHF1 in cytoplasm of glomerular mesangial cells (arrows). b Electron microscopy shows structural relationship of mesangial cells (MC) with other cells and glomerular basement membrane (GBM). c Western blot shows PHF1 in the cerebral cortex and isolated glomeruli of WT or Il33^−/− mice at 70 weeks; note an additional band of low molecular weight of PHF1 (arrow) among glomerular proteins, which is absent in cortical proteins. d RT-PCR shows a lack of tau mRNA in glomeruli as compared to the cortex in both WT and Il33^−/− mice. e Immunohistochemistry on PHF1 in the cerebral cortical and glomerular tissue from the same representative WT or Il33^−/− mice reveals a reverse correlation between PHF1 in the two tissue locations, i.e., more neuronal PHF1 vs less glomerular PHF1 (arrows) in Il33^−/− mice, and vice versa in WT mice. f Statistical analysis shows a positive regression between glomerular PHF1 and cortical AQP4 among WT and Il33^−/− mice. IOD, integrated optical density. g Immunofluorescence on normal human kidneys reveals the presence of PHF1, but not phospho-tau(Ser202/Thr205) (AT8), in glomeruli; an isotype IgG control is also shown; numbered boxed areas are enlarged to show PHF1 in mesangial cells. Bars’ unit = μm.