BACKGROUND: In proteinuric @entity8 with increasingly severe defects of the glomerular filtering barrier, interstitial fibrogenesis is a major effector of scarring. An early event in this process is the peritubular accumulation of myofibroblasts that express @entity1918 ( @entity1918 ) and contribute to abnormal matrix production. Common trigger factors are poorly understood. Enhanced protein trafficking may play a role by up-regulating inflammatory and fibrogenic genes in proximal tubular cells. METHODS: The remnant kidney model in @entity35 was used to (1) analyze interactions between activated proximal tubular cells, peritubular cells expressing the myofibroblast marker, and inflammatory cells at time intervals (days 7, 14, and 30) after surgery, and (2) evaluate the effects of angiotensin-converting enzyme inhibitor (ACEi) on protein trafficking, fibrogenic signaling, and @entity1918 expression. RESULTS: Abnormal uptake of ultrafiltered proteins by proximal tubular cells (IgG staining) occurred at an early stage (day 7) and was subsequently associated with macrophage and @entity1918 + cell accumulation into the peritubular interstitium. @entity1918 + cells clustered with macrophages into the interstitium. These changes were associated with appearance of @entity1810 ( @entity1810 ) mRNA in proximal tubular cells and in the infiltrating cells with time. At day 30, focal @entity1918 staining also was found in the tubular cells and in peritubular endothelial cells on semithin ultracryosections. ACEi prevented both @entity644 and abnormal protein accumulation in tubular cells, as well as the inflammatory and fibrogenic reaction with peritubular @entity1918 expression. CONCLUSIONS: Profibrogenic signaling from both proximal tubular cells on challenge with filtered protein and inflammatory cells is implicated as a key candidate trigger of progressive @entity130 .

Proximal tubular cells promote fibrogenesis by XXXX -mediated induction of peritubular myofibroblasts.

@entity644 :: ('MESH:D011507', 'Disease') :: ['proteinuria'] @entity8 :: ('MESH:D007674', 'Disease') :: ['nephropathies'] @entity1918 :: ('25365(Tax:10116)', 'Gene') :: ['alpha-SMA', 'alpha-smooth muscle actin'] @entity1810 :: ('59086(Tax:10116)', 'Gene') :: ['TGF-beta1', 'transforming growth factor-beta1'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity130 :: ('MESH:D014947', 'Disease') :: ['tubulointerstitial injury']
@entity1810 :: (59086(Tax:10116),Gene) :: ['TGF-beta1']
