UUO

1. Fig 1, Bascands & Schanstra cellular infiltration myofibroblast accumulation tubular atrophy ECM infiltration UUO EMT apoptosis proliferation proliferation - + ECM Collagen production fibroblast growth factors/cytokines epithelial cell macrophage apoptotic cell myofibroblast

2. Fig 2, Bascands & Schanstra CCR1 CD44 circulation endothelial cells L-selectin chemokines osteopontin sulfatide interstitium

3. Fig 3, Bascands & Schanstra TGF Interstitial fibroblast activation Epithelial Mesenchymal Transition 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 tubule fibroblast myofibroblast MMP9 expression Bone marrow derived cells matrix accumulation tPA knockout interstitium

4. Fig 4, Bascands & Schanstra matrix PAI-1 MMP plasmin PA angiotensinogen kininogen renin ACE-inhibitors kallikrein AI bradykinin TGF AII ACE AT1 receptor inactive peptides cellular infiltration HGF plasminogen B2 receptor pro-MMP matrix MMP-9 EMT

5. Fig 5, Bascands & Schanstra P IB IB NF-B NF-B NF-B angiotensinogen renin AI ACE AII TNFa postive regulation loops AT1 AT2 TNFR1 TNFR2 IB kinases TNFa angiotensinogen gene transcription inflammation matrix expression proinflammatory and profibrotic cytokines IkB degradation NF-kB motif Nucleus fibrosis

6. Fig 6, Bascands & Schanstra R-I R-I R-II R-II TGF TGF TGF P SMAD2/3 P SMAD2/3 P SMAD4 decorin R-I SMAD2/3 R-II RhoA/Rock stress fiber formation p38MAPKs reorganization of actin cytoskeleton plasmin integrin aVb6 SMAD4 Nucleus gene transcription EMT cellular infiltrationapoptosis enhancer of TGFb regulated genes latent-TGF Tubulointerstitial fibrosis