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. 2021 Jul 20;11:14789. doi: 10.1038/s41598-021-93034-w

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© The Author(s) 2021

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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Cellular and metabolic gene expression changes correlate with expression of genes indicating tubular damage in human and murine LN. Log2 expression of (a) HAVCR1/Havcr1 and (b) LCN2/Lcn2 in human LN TI and the kidneys of (NZM2410 (GSE32583, GSE49898), NZB/W (GSE32583, GSE49898), IFNα-accelerated NZB/W (GSE86423), IFNα-accelerated NZB/W (GSE72410), and MRL/lpr (GSE153021) mice. Each point represents an individual human or mouse. Significant differences in gene expression at each timepoint compared to disease were evaluated in the human TI with Welch’s t-test and in murine models with the Mann–Whitney U test. Linear regression between HAVCR1/Havcr1 and LCN2/Lcn2 expression and kidney cell, proximal tubule, and TCA cycle GSVA scores in all samples for (c–e) human and (f) murine LN. For all calculations the following sample numbers were used: LN TI [CTL (n = 15), Cl II (n = 8), Cl III/IV (n = 22)], NZM2410 [6w (n = 5), 21-30w (n = 5), Tx + 15w (n = 6)], NZB/W [16w (n = 8), 23w (n = 6), 36w (n = 10), Tx Remission + 3-4w (n = 8), Tx Remission + > 5w (n = 6)], IFN-accelerated NZB/W (GSE86423) [Baseline (n = 3), W1 (n = 5), W2 (n = 5), W3 (n = 5), W5 (n = 5), W7 (n = 5), and W9 (n = 5)], IFN-accelerated NZB/W (GSE72410) [Naïve (n = 5), IFN W3 (n = 5), IFN W7 + Veh (n = 5), IFN W7 + CTX (n = 5)], and MRL/lpr [Wildtype (n = 3), Vehicle (n = 3), Prednisone (n = 3), MMF (n = 3), FK506 (n = 3), Multi-target (n = 3)]. Significant p-values in (c–f) reflect significantly non-zero slopes determined by linear regression or correlation analysis. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.