Andrea Wong

"Regulation of intestinal ACE2 expression by dsRNA"

Andrea Wong, Patrick Lundgren, Oxana Dmitrieva-Posocco, Lenka Dohnalová, Aleksandra Golos, Lilian Sun, Zoe Steinberg, Timothy Cox, Peter Hewins, Mark Dittmar, Kellie Jurado, Sara Cherry, Christoph A. Thaiss, Maayan Levy

The intestinal microbial community and the pattern associated molecular patterns (PAMPs) it produces play a vital role in modulating host immunity and gene expression. Identifying microbial modulators of key host genes involved in intestinal homeostasis can lend significant insight into the ways the microbiome shapes host physiology. This project began out of an observation made by our lab that disruption of the microbiome results in increased angiotensin-converting enzyme 2 (ACE2) expression in the small intestine.  We found that germ free mice have significantly higher intestinal ACE2 mRNA and protein expression compared to conventionally housed mice. This data suggests that some microbial element suppresses ACE2 expression in the intestine. The microbiome is composed of commensal bacteria, fungi, protozoa, and viruses which co-exist with the host. Our lab has identified a synthetic double-stranded RNA viral analogue, poly(I:C) as a negative regulator of ACE2 expression in enterocytes. Preliminary data from our lab suggests dsRNA regulation of ACE2 is dependent on NFkB and TNF- signaling.
Microbial regulation of ACE2 is of particular interest because of the role ACE2 plays in host physiology and immunity. ACE2 has a number of different important physiological functions including regulation of the renin-angiotensin system (RAS) and absorption of neutral amino acids in the small intestine, namely tryptophan. Furthermore, ACE2 is the host receptor for SARS-Co-V-2 virus. Our preliminary data suggests that all these physiological processes may be regulated via ACE2 by the microbiome and viral sensing.