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Fig 1, Bascands & Schanstra cellular infiltration myofibroblast accumulation tubular atrophy epithelial cell + ECM macrophage apoptotic cell fibroblast myofibroblast growth factors/cytokines Collagen production Fig 2, Bascands & Schanstra CCR1 CD44 L-selectin chemokines osteopontin sulfatide endothelial cells Fig 3, Bascands & Schanstra TGF Interstitial fibroblast Epithelial Mesenchymal Transition tubule MMP9 expression tPA knockout 1) Loss of epithelial adhesion properties 2) a-SMA expression and actin reorganization 3) Disruption of the tubular basement membrane 4) Enhances epithelial cell migration and invasion fibroblast Bone marrow derived cells interstitium myofibroblast matrix accumulation Fig 4, Bascands & Schanstra angiotensinogen kininogen kallikrein renin ACE-inhibitors bradykinin AI AII inactive peptides matrix TGF AT1 receptor cellular infiltration B2 receptor plasminogen plasmin pro-MMP MMP MMP-9 matrix EMT Fig 5, Bascands & Schanstra AI AII renin angiotensinogen ACE TNFa AT1 AT2 TNFR1 TNFR2 IB kinases IB IB P NF-B NF-B IB degradation gene transcription NF-B motif Nucleus TNFa angiotensinogen proinflammatory and profibrotic cytokines inflammation matrix expression fibrosis Fig 6, Bascands & Schanstra decorin R-I SMAD2/3 R-II SMAD2/3 plasmin integrin aV6 SMAD4 RhoA/Rock p38MAPKs P stress fiber formation reorganization of actin cytoskeleton Nucleus gene transcription EMT cellular infiltration apoptosis enhancer of TGF regulated genes latent-TGF Tubulointerstitial fibrosis
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