ACE2 cleaves Angiotensin II, regulates inflammation, and mediates coronavirus entry.

• Gene Information: The ACE2 gene, mapping to chromosome X, encodes a type I transmembrane metallocarboxypeptidase that is a critical counter-regulatory component of the renin-angiotensin-aldosterone system (RAAS).
• Protein Expression: ACE2 is abundantly expressed on the surface of vascular endothelial cells, renal tubular epithelium, and gastrointestinal enterocytes, with particularly prominent expression on type II alveolar pneumocytes in the lungs.
• Signaling Pathway: Functionally, ACE2 cleaves pro-inflammatory Angiotensin II into the vasodilatory and anti-inflammatory Angiotensin-(1-7), which subsequently activates the Mas receptor pathway to counteract the detrimental, hypertensive effects of the conventional ACE/Angiotensin II/AT1R axis.
• Therapeutic Inhibition: Therapeutic strategies targeting ACE2 primarily focus on deploying recombinant human ACE2 (rhACE2) or small molecules to block the entry of coronaviruses-which utilize ACE2 as a functional receptor for cell fusion-or to restore RAAS balance in cardiovascular and pulmonary diseases.

ACE2

• The 2 copies of full coding sequences of human ACE2 gene linked by the P2A, including the human cytokeratin 18 promoter (K18), K18 3’UTR are inserted into mouse Hipp11 (H11) locus in B-hACE2 mice.

• Mouse Ace2 mRNA was detectable both in B-hACE2 mice and wild-type mice as the murine Ace2 was remained. Human ACE2 mRNA was detectable only in homozygous B-hACE2 mice but not in wild-type mice.

Strain specific analysis of ACE2 mRNA expression in wild-type C57BL/6JNifdc mice and B-hACE2 mice by RT-PCR. Kidney RNA was isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hACE2 mice (H/H), and then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human ACE2 primers.

• Human ACE2 was detectable only in homozygous B-hACE2 mice and Caco-2 cell line but not in wild-type C57BL/6JNifdc mice.

Western blot analysis of ACE2 protein expression in wild-type C57BL/6JNifdc mice and homozygous B-hACE2 mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hACE2 mice (H/H), and then analyzed by western blot with ACE2 antibody[EPR4436] (Abcam, ab108209). 40μg total proteins were loaded for western blot analysis.