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. 2022 Aug 27;13:5062. doi: 10.1038/s41467-022-32477-9

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© The Author(s) 2022

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — a Experimental scheme: 16 weeks after induction of persistent hyperglycemia, diabetic mice were treated with PBS (DM + PBS), sodium/glucose cotransporter 2-inhibitor (Dapagliflozin®, DM + SGLT2i), a combination of SGLT2i and 3K3A-aPC (DM + SGLT2i + 3K3A-aPC) or a combination of SGLT2i, aPC and parmodulin-2 (DM + SGLT2i + Parm.) for further 6 weeks. b Average blood glucose levels after 8 and and16 weeks of persistent hyperglycemia and at 22 weeks in experimental groups (as described in a). c Dot plot summarizing albuminuria (urinary albumin-creatinine ratio, µg albumin/mg creatinine; UACR) in experimental groups (as described in a). Baseline albuminuria before interventions was determined after 16 weeks of hyperglycemia (DM-16). d–f Expression of renal p21 mRNA (Cdkn1a, qRT-PCR, d; and protein, f), renal DNMT1 mRNA (Dnmt1, qRT-PCR, e), and renal KIM-1 (protein, f) in experimental groups (as described in a). Exemplary immunoblots (f; GAPDH: loading control). g Exemplary histological images of periodic acid Schiff stain (PAS), interstitial fibrosis (Masson’s trichrome stain, MTS), SA- β-gal. stain (senescence associated β-galactosidase), and γ-H2A.X (histone H2A, family X, red, immunofluorescent, DAPI nuclear counterstain, insets: larger magnification) in experimental groups (as described in a); all scale bars represent 20 μm. Line graph or dot plots reflecting mean ± SEM of six mice per group; one-way ANOVA with Sidak’s multiple comparison test. Gels/blots were processed in parallel; source data are provided as a Source Data file-Fig-8.