Conversely, in dual ACE2 and Mas receptor–deficient mice, Ang II–induced hypertension resulted in severe hypertensive nephropathy, which was associated with decreased creatinine clearance and increased renal fibrosis, inflammation, and AT1 receptor-ERK1/2-Smad3 and NF-κB signaling (Ni et al., 2020). This evidence concerns the gene MAPK3 and renal fibrosis.