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. 2022 Dec 23;13:7907. doi: 10.1038/s41467-022-35590-x

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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. 3 — a Comparison of MMP14 expression levels in lung and airway cells from uninfected populations and patients infected with SARS-CoV-2. Boxplots show the median (central line), the 25–75% interquartile range (IQR) (box limits), the ±1.5 × IQR (whiskers). (n = 44 for healthy controls; n = 104 for infected patients) b MT1-MMP promotes the entry of SARS-CoV-2 viral pseudotypes in host cells. HEK293T cells expressing different ACE2 mutants (wild-type ACE2, ACE2 S707A & ACE2 I727A) were transfected with WT or E/A catalytic mutant MT1-MMP (MT1 E240A) and infected with SARS-CoV-2 viral pseudotypes for 72 h. Intracellular luciferase levels were measured. (n = 3) c ACE2-HEK293T cells were inoculated with various concentrations of conditioned media derived from HEK293T transfected with ACE2 with/without MT1-MMP, followed by infection with SARS-CoV-2 pseudotypes for 72 h. Intracellular luciferase levels were measured. (n = 3) d, e Huh-7 or Caco2 cells were transfected with either siRNA targeting MMP14 or control siRNA, followed by the infection with SARS-CoV-2 pseudotyped virus. Luciferase levels were detected by chemiluminescence at 72 h post-infection. (n = 3) (p=<2e-16) f Caco2 cells stably transduced with shMMP14 or control shRNA were infected with SARS-CoV-2 pseudotyped virus for 48 h. The expression levels of solACE2, memACE2 and MT1-MMP were subsequently detected by western blotting. (n = 3) g The HK-2 cells were inoculated with the conditioned media derived from HEK293T cells co-expressing either ACE2, ACE2 with MT1-MMP or ACE2 with catalytic mutant MT1-MMP (E240A), followed by SARS-CoV-2 infection. (n = 3) h The HK-2 cells pretreated with different concentrations of recombinant ACE2 and with or without incubation with catalytic domain of MT1-MMP were infected with SARS-CoV-2. Mock-treated HK-2 cells served as a control. (n = 3) i Primary human bronchial epithelial 3D cultures with an air-liquid interface (ALI) were lentivirally transduced with shRNA targeting MT1-MMP or control shRNA, following by the infection of SARS-CoV-2. (n = 3) The data are shown as the means ± SEM from three independent experiments. P values were calculated using one-way ANOVA for (b, e; g, h); two-way ANOVA for (i) and unpaired two -tailed t-test for (a). Source data are provided as a Source Data file.