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. 2021 Dec 2;23(2):e53658. doi: 10.15252/embr.202153658

Figure 5. Selective inhibition of telomeric DDR decreases ACE2 expression in cultured cells and in vivo .

Figure 5

  1. Immunofluorescence showing γH2AX foci in Trf2F/F MEFs at the indicated time points following 4OHT treatment and consequent TRF2 knockout and treated with DMSO or ATMi. Scale bar, 25 µm.
  2. RT‐qPCR detection of Ace2 mRNA expression levels in MEFs Trf2F/F treated as in A (n = 3 independent experiments).
  3. Representative immunofluorescence images of 53BP1 staining in liver from Trf2F/F mice treated with tamoxifen (to induce telomere uncapping) or vehicle and injected with the indicated ASOs or PBS as control. Scale bar, 10 µm.
  4. RT‐qPCR detection of Ace2 mRNA levels in livers of mice treated as in C (n = 5–8 mice per group).
  5. Representative microphotographs and quantitative analyses of ACE2 immunohistochemical staining in lungs of age‐matched wild‐type and G3 Terc−/− mice, treated with the indicated ASOs (n = 4–9 mice per group). Scale bar, 200 µm.
  6. Double‐marker immunofluorescence and quantitative analyses of ACE2 intensity level in pro‐SP‐C‐positive type II pneumocytic cells in lungs of age‐matched wild‐type and G3 Terc−/− mice, treated with the indicated ASOs (n = 4–9 mice per group). Scale bar, 100 µm. a.u. = arbitrary units.

Data information: In (B, D–F), data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ***P < 0.0001. Two‐way paired (B) or unpaired (D‐F) ANOVA.