SARS-CoV FIBROSIS

Pulmonary fibrosis is a common consequence of SARS coronavirus (SARS-CoV) infection. Transforming growth factor-β1 (TGF-β1) is a crucial mediator of this phenomenon and causes tissue fibrosis by activating downstream small mother against decapentaplegic (Smad) signaling which triggers pro-fibrotic genes overexpression. Smad3 is the major downstream regulator that promote TGF-β mediated tissue fibrosis, while Smad7 protects against fibrosis inhibiting the TGF-β1/Smad pathway. The renin-angiotensin system (RAS) also controls the fibrotic process. The Spike-dependent down-regulation of ACE2 receptor decreases the Ang (1-7) level, upregulating the angiotensin-converting enzyme (ACE)- Ang II-angiotensin type 1 receptor (AT1R) signalling cascade, which in turn triggers inflammation and fibrosis in pulmonary tissue.