Accordingly, in kidneys, TGF-β1/Smad3-P signaling regulates the transition of BM-derived macrophages into myofibroblasts, leading to inflammation and tissue fibrosis43,44 and CD206-positive M2-macrophages are strongly associated with renal fibrosis, both in humans and in experimental diseases44. This evidence concerns the gene SMAD3 and renal fibrosis.