SMAD2 and fibrosis: Conversely, Serpine1 modulates key pathways: it controls abdominal aortic aneurysm formation via TGF-β/Smad2/3 signaling (Zhao et al., 2025), influences macrophage polarization to reduce cardiac fibrosis in inflammatory cardiomyopathy, and suppresses inflammation in experimental autoimmune encephalomyelitis (EAE) by inhibiting Th1 cell secretion of IFNγ and TNFα (Akbar et al., 2023).