Our new paper on the regulation of ACE2 is out in @Dev_Cell:
Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract.
cell.com/developmental-…
Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract.
cell.com/developmental-…
In short: smoke exposure increases the number of MUC5AC+ lung secretory cells that express ACE2. Quitting smoking decreases secretory cell abundance and lowers ACE2 levels. Viral infections also cause a significant increase in ACE2, which may be due to interferon signaling.
One aspect of publishing that I really appreciated: @Dev_Cell has added a manuscript section entitled “Limitations”, where you can discuss the potential limitations of your work and directly consider alternate explanations. I’d love to see this widely adopted in other journals.
For instance - we show that ACE2 mRNA and protein levels tend to be tightly correlated - but we discuss how this doesn’t prove that that is necessarily the case for smokers, or that all ACE2 protein is localized to the cell surface and available for Spike binding.
Some key questions remaining that we hope to address: how important are ACE2 levels for SARS-CoV-2 susceptibility? Could ACE2 expression have a protective effect during infections? And does infection-mediated inflammatory signaling promote SARS-CoV-2 dissemination?
It seems like the journal pre-proofs do not include the supplemental figures, but a nearly-final version was posted with our last preprint: biorxiv.org/content/10.110….
This work was led by my partner @joans, whose brilliance and insight never stop amazing me.
