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. 2020 Jun 25;10:10345. doi: 10.1038/s41598-020-67217-w

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© The Author(s) 2020

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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Systemic midkine (MK) knockdown effects on pulmonary arterial remodeling in chronic hypoxia-induced pulmonary arterial hypertension (PAH) mice. (a) Representative Elastica-Masson staining images of mouse lung transverse sections at 4 weeks after the exposure to normoxia or hypoxia. Scale bars, 50 µm. (b) Degree of muscularization of pulmonary arterial vessels (outer diameter 20–100) in mice exposed to normoxia or hypoxia (n = 5–9 each). WT, wild-type mice; MK-KO, midkine knockdown mice. (c) Pulmonary arterial remodeling evaluated by the percentage of medial wall thickness (n = 5–9 each). (d) Right hypertrophy [ratio of right ventricle (RV)/left ventricle plus septum (LV + S)] (n = 5–9 each). (e) Pulmonary artery acceleration time (PAAT)/ pulmonary artery ejection time (PAET), determined by echocardiography (n = 5–15 each). (f) Western blots analysis of EGFR and ERK1/2 phosphorylation rates in mouse lungs (n = 5). Full-length blots are presented in Supplementary Figure 2. (g) Western blots analysis for Ccnb1, PCNA, and β-tubulin levels in mouse lungs (n = 5). Full-length blots are presented in Supplementary Figure 3. *ANOVA post-hoc Tukey’s honest significant difference, P < 0.05, compared with the indicated control.