Fig. 5: Proximal tubular Vhl deletion resets all genes altered upon induction of DKD by reduced H3K4me3 histone modification.

A and B Heat maps of significantly commonly altered genes of VHLΔPT + con/STZ + VHLΔPT/STZ (HIF-1α related) vs. control (A) and remaining HIF-1α unrelated genes altered in con/STZ vs. control (B). Filter criteria DESeq P-values < 0.05, fold-change > 1.5. C Gene ontology analysis of VHLΔPT and VHLΔPT/STZ vs. control; top 23 biological processes enriched/depleted in the corresponding comparisons. In addition, processes containing the term “chromatin modification” are presented in green, and “insulin“is shown in orange, if significant. D STRING network analysis of Gene ontology analysis underlying genes, including Ash1l, Ogt, Kmt2a, Uty, Kmt2d, Kmt2c, Ep300, Kat6a, Arid4b, Prkaa2, Kmt2e, Kdm5a, Kdm1b, Arid5b, Baz2a, Huwe1, Atxn7. Hif-1α is identified as a functional interaction partner (red circle). E and F Representative blot, densitometrical evaluation, and immunohistochemical images of H3K4me3 double stained with megalin to mark proximal tubules obtained from control, VHLΔPT, con/STZ and VHLΔPT/STZ with histone H3 as reference. Arithmetic means ± SEM of n = 5–7 per group; *P < 0.05. Scale bar = 50 µm. F G: glomeruli. Each point represents an individual mouse. Nonparametric Kruskal–Wallis with Dunn’s post-test.