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Pathogenesis of tubulointerstitial fibrosis in obstructive nephropathy. This pathogenesis has been extensively studied. Increased expression of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and the angiotensin II type 1 (ATI) receptor occurs in the obstructed kidney. Angiotensin II can induce the synthesis of transforming growth factor p (TGF-p), a cytokine that stimulates extracellular matrix synthesis and inhibits its degradation. Obstructive nephropathy is accompanied by downregulation of the kallikrein-kinin system and nitric oxide production that can be reversed by administration of a converting enzyme inhibitor or of L-arginine. The rapid upregulation of chemotactic factors such as monocyte chemoattractant peptide 1 (MCP-1) and osteopontin in the tubular epithelial cells, in response to increased intratubular pressure, contributes to the recruitment of macrophages. Macrophages produce fibroblast growth factor and induce fibrob-last proliferation and myofibroblast transformation. The downregulation of epidermal growth factor (EGF), Bcl 2, and antiox-idant enzymes and the increased production of superoxide and hydrogen peroxide (H2O2) contribute to an increased rate of apoptosis and tubular dropout [51- 57]. PDGF-platelet-derived growth factor; SOD—superoxide dismutase; TIMP—tissue inhibitor of metalloproteinases.

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