SMAD2 and lung adenocarcinoma: For example, in lung adenocarcinoma A549 cells, TGF-β1 induces upregulation of SDC-4, leading to enhanced cell proliferation, migration, and EMT.76 Conversely, the SDC-4 KO mouse exhibited a significant reduction in aristolochic acid nephropathy-induced recruitment of TGF-β1 in the kidney and less fibrosis.77 We found that after injury, compared with WT mice, SDC-4 KO mice exhibited higher expression level of epithelial marker, lower expression levels of mesenchymal markers, and reduced phosphorylation of Smad2, suggesting that SDC-4 also contributes to TGF-induced EMT of LECs.