TNF and Myocardial fibrosis: However, studies on the role of S100A4 and p53 in myocardial fibrosis revealed that the expression of S100A4 and p21, a downstream gene of p53, in myocardial stromal fibroblasts is regulated by Smad3 and Bmal1 through tumor necrosis factor-α (TNF-α) (Sato et al. 2017).