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. 2024 Sep 11;15:7963. doi: 10.1038/s41467-024-52214-8

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Experimental scheme of the DKD model. Wild type (WT) and F12^-/- mice were age-matched, and persistent hyperglycemia was induced using streptozotocin (STZ) for 24 weeks. b Exemplary histological images of kidney sections stained for FXII comparing normoglycemic controls (C) and hyperglycemic (DM) WT and F12^-/- mice. FXII is detected by HRP-DAB reaction (brown); hematoxylin nuclear counter stain (blue). Scale bars represent 20 μm. c Line graphs showing urinary albumin-creatinine ratio (UACR, μg albumin/mg creatinine) in experimental groups (as described in b) after 8, 16, or 24 weeks of persistent hyperglycemia. Line graphs reflecting mean ± SEM of 6 mice per group; two-way ANOVA with Tukeys’s multiple comparison test comparing hyperglycemic WT and F12^-/- mice at the 3 time points. d, e Dot-plots summarizing blood urea nitrogen (BUN, mmol/l; (d) and adjusted kidney weight (KW/BW, mg kidney weight /g body weight; (e) in the experimental groups (as described in b). Dot-plots reflecting mean ± SEM of 6 mice per group; two-way ANOVA with Tukeys’s multiple comparison test. f Exemplary histological images of periodic acid Schiff staining (PAS) showing glomeruli (top panel), podocyte number reflected by Wilms tumor 1 immunostaining (WT-1, brown, hematoxylin nuclear counterstain, blue; middle panel), and transmission electron microscopy of podocytes (TEM; bottom panel) in experimental groups (as described in b); scale bars of top and middle panels represent 20 μm, while scale bars of bottom panel represent 1 μm. g Exemplary histological images of periodic acid Schiff staining (PAS) showing tubuli (top panel), interstitial fibrosis (middle panel, Masson’s trichrome stain, MTS), and kidney injury molecule-1 immunostaining (bottom panel, KIM-1, red; DAPI nuclear counterstain, blue) in experimental groups (as described in b); all scale bars represent 20 μm. Source data are provided as a “Source Data” file.