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. 2022 Sep 29;13:976512. doi: 10.3389/fimmu.2022.976512

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Copyright © 2022 Zhang, Tang, Zhang, Tong, Xie, Yan, Wang, Zhang, Liu and Li

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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EndMT proportion is upregulated in COVID-19. (A) The expression of pulmonary ECs in patients with health control, COVID-19, IPF was demonstrated using UMAP plots with subpopulations marked by a color code. ECs subpopulations including rest ECs, EndMT, DKK2 ⁺ ECs, activated ECs; Lymphatic ECs. (B) Dot chart shows the marker of EndMT, mainly focusing on ACTA2, MMP2, COL3A1; rest ECs (IL7R, CA4), DKK2 ⁺ ECs (DKK2), activated ECs (ACKR1); Lymphatic ECs(PROX1,PDPN). (C) Proportion of ECs among normal control group, COVID-19 group and IPF group, the ratio of EndMT was increased in COVID-19 and IPF than controls. One-way ANOVA was used to compare multiple groups (p<0.05). (D) Heatmap shows a comparison of the expression of major cytokines in the cell subpopulations of ECs shows that EndMT is enriched in more cytokines compared to the other groups. (E) Comparison of the ratios of HC, COVID-19, IPF subpopulations of ECs by gender in nonsmokers. EndMT ratio in females is lower than that in males with COVID-19. (F) Comparison of entry factors (ACE2, BSG, FURIN, CTSL, TMPRSS2) positive cell fraction in ECs subtype of COVID-19 and IPF. (G) Comparison of EndMT proportion of entry factors (BSG, FURIN, CTSL) in HC, COVID-19, IPF. (H) Forest plot of studies with lung scRNA data on the COVID-19, after excluding a study with only one case and a high heterogeneity study. The analysis included data from 3 studies with a total of 48 COVID-19 and 34 controls. p value for heterogeneity was 0.18, I² was 42%. (SD: Standard deviation). (I) Ratio of myofibroblasts in COVID-19 and IPF for EndMT ^low versus EndMT ^high, showing myofibroblast ratio in EndMT ^high is higher than that in EndMT ^low. (J) A comparison of the expression of major cytokines in the EndMT shows that COVID-19 and IPF are enriched in more profibrotic cytokines compared to HC group. (K) Correlation analysis of EndMT with myofibroblast, rest fibroblast and profilerative fibroblast in COVID-19 and IPF patients (Pearson test), showing EndMT is positively correlated with myofibroblasts in COVID-19 patients. *P < 0.05, **P < 0.01, ***P < 0.001,****P < 0.0001.