SMAD3 and diabetic kidney disease: The fibrotic microenvironment in DKD is shaped by cell death-specific factors: (1) Pyroptotic cells release IL-1β → induce epithelial-to-mesenchymal transition (EMT) in tubular cells by transforming growth factor beta/SMAD family member 3 (TGF-β/Smad3) and Snail1 upregulation; (2) Necroptotic cells release HMGB1 and ATP → activate NLRP3 in macrophages → secrete platelet-derived growth factor (PDGF) and connective tissue growth factor (CTGF); (3) Ferroptotic cells: Generate oxidized phospholipids → directly stimulate fibroblast proliferation through 12-lipoxygenase (LOX-12) activation.