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. 2022 Oct 26;13:6371. doi: 10.1038/s41467-022-33734-7

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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. 1 — a, b Postnatal 1 day (P1) wild-type mice underwent heart apical resection (AR) or Sham surgery. The regenerating hearts were collected at P3, P7, P14, and P21. a Western blot assay and quantification showing the expression profiles of tryptophan-kynurenine (Trp-Kyn, TK) metabolic mediators during heart regeneration (n = 6/stage). b Kyn and Trp levels measured by HPLC. *P < 0.05 vs. the Sham group at the indicated times (n = 6/stage). c–f Ido1 ^F/F (Ido1 ^Flox/Flox) and Ido1 ^mKO (Tnt ^Cre; Ido1 ^Flox/Flox) mice underwent AR or Sham surgery at P1 and heart was collected at P21 for HPLC, Masson staining and echocardiography assay. c Representative images and quantitation of fibrosis area by Masson staining (n = 6 for Sham Ido1 ^F/F and Sham Ido1 ^mKO; n = 8 for AP Ido1 ^F/F and AP Ido1 ^mKO). Bar = 500 µm. d Cardiac Kyn level measured by HPLC assay (n = 6/group). e, f left ventricular ejection fraction (LVEF, e) and fractional shortening (LVFS, f) analyzed by echocardiography (n = 7/group). g Cardiomyocyte (CM) proliferation assessed by co-staining of KI67 or PH3 with Troponin T (TNT) at P7 (n = 6/group). Bar = 20 µm. Data are mean ± SD. *P < 0.05 by two-way ANOVA followed by Tukey’s multiple comparisons test in (a, b), one-way ANOVA followed by Tukey’s multiple comparisons test in c (P = 0.0002), d (P < 0.0001), e (P = 0.178), f (P = 0.042), and g (P = 0.0005 for KI67 and P = 0.0029 for PH3).