Fig. 2

ACE2 signaling network. A ACE2 interacts with several molecules, including S-protein. B The role of ACE2 in lung fibrosis. TGF-β1 is an essential mediator of fibrosis by activating downstream “SMAD” signaling, which triggers pro-fibrotic genes overexpression. Smad3 is the central canonical mediator for fibrogenesis, while Smad7 negatively regulates the fibrosis process. The RAS also controls the fibrotic process. Down-regulation of ACE2 decreases the angiotensin 1–7 level, upregulating the AT1R signaling cascade, which in turn triggers fibrosis (Data source: https://signor.uniroma2.it/)