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. 2023 Oct 14;14:6493. doi: 10.1038/s41467-023-42154-0

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© The Author(s) 2023

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 Whole-kidney lysates from Umod ^+/+ (n = 3) and Umod ^DEL/+ (n = 4) mice at 12 weeks were analyzed by WB for p50ATF6 (arrow) with densitometry analysis. Two-tailed t-test, Mean ± SD. *p = 0.0376. b WBs of whole-kidney lysates (WT, n = 4; Umod ^DEL/+, n = 6) at 16 weeks to detect the autophagy mediators p62 and LC3B with densitometry analysis. Two-tailed t-test, Mean ± SD. *p = 0.016 (for p62), 0.049 (LC3B-II). c, d RNA-seq analysis of mutant and WT TALs at 16 weeks. n = 5/group. Benjamini-Hochberg adjusted p < 0.05. c KEGG pathway analysis of the log2 fold-changes in TAL cells showed the top 22 downregulated pathways. GAGE analysis. d RNA-seq analysis of genes for autophagy, ER stress response, inflammation, apoptosis, kidney injury and fibrosis in the mutant TALs compared with WT TALs. Limma analysis for differential gene expression. e WB from Umod ^+/+ (n = 3) and Umod ^DEL/+ (n = 4) kidneys for levels of p-mTOR (S2481) at 12 weeks with densitometry analysis. Two-tailed t-test, Mean ± SD. **p = 0.0081. f WBs from Umod ^+/+ (n = 3) and Umod ^DEL/+ (n = 4) TALs for levels of FOXO3 and p-AMPK (arrow) at 12 weeks with densitometry analysis. Two-tailed t-test, Mean ± SD. ****p < 0.0001. g Transcript analysis of a panel of autophagy and mitophagy-related genes, normalized to 18 s, from TALs at 12 weeks. WT (n = 3) and Umod ^DEL/+ (n = 5) for Ulk1, Gabarapl1, Atg7, Pink1 and Bnip3; WT (n = 5) and Umod ^DEL/+ (n = 7) for Becn1, Atg5 and Map1lc3b. Two-tailed t-test, Mean ± SD. p = 0.02 (for Ulk1), 0.0027 (Becn1), 0.0034 (Atg5), 0.0079 (Gabarapl1), 0.0006 (Atg7), 0.0039 (Map1lc3b), 0.0032 (Pink1), 0.0005 (Bnip3). h Representative IF images of human kidney biopsies obtained from a patient with p.H177-R185 del and from a normal kidney, stained for p62 (green) and UMOD (red) with nuclei counterstain (blue) on paraffin kidney sections. Scale bar, 40 µm. Source data are provided as a Source Data file.