SARS‐CoV‐2 N protein‐induced AKI is associated with activation of Smad3‐p21‐dependent G1 cell cycle arrest pathway. A) Western blotting for activation of Smad3 (p‐Smad3) and expression of p21 and cyclin E. B) Real‐time PCR for levels of SARS‐CoV‐2 N, p21, and cyclin E mRNA expression. C) Immunohistochemistry for detecting SARS‐CoV‐2 N protein expression, activation of Smad3 (p‐Smad3 nuclear translocation), and cell apoptosis by TUNEL‐labeling. Note that overexpressing SARS‐CoV‐2 N in the normal mouse kidney resulted in a marked activation of Smad3, upregulation of p21 while inhibiting cyclin E, and a massive cell apoptosis. Each dot represents one mouse and data are expressed as the mean ± SEM for groups of six mice. #p < 0.05, ##p < 0.01, ###p < 0.001 versus empty vector control (VC‐Day2) group. g, glomerulus; scale bars = 50 µm.