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- Title
Paracrine stimulation of human renal fibroblasts by proximal tubule cells<sup>1</sup>.
- Authors
Johnson, David W.; Saunders, Heather J.; Baxter, Robert C.; Field, Michael J.; Pollock, Carol A.
- Abstract
Paracrine stimulation of human renal fibroblasts by proximal tubule cells. Background . Interstitial fibrosis strongly predicts the degree and progression of renal failure in human renal disorders. Since active fibrosis tends to initially occur in a peritubular distribution, the possibility that human proximal tubule cells (PTC) relay fibrogenic signals to neighboring cortical fibroblasts was examined in vitro . Methods . Cell proliferation (cell counts and thymidine incorporation), total collagen synthesis (proline incorporation), matrix metalloproteinase (MMP) activity (gelatin zymography), and autocrine secretion of insulin-like growth factor-I (IGF-I) were measured in primary cultures of human cortical fibroblasts cocultured with PTC or exposed to PTC-conditioned media (PTC-CM). Results . Cell numbers and thymidine incorporation rates were increased in cortical fibroblasts cocultured with PTC (136.4 ± 7.3% and 119.3 ± 8.2% of control values, respectively, P < 0.05) or incubated in PTC-CM (114.0 ± 5.9%, P < 0.05 and 146.7 ± 13.3%, P < 0.05, respectively). PTC-CM stimulated cortical fibroblast collagen synthesis (13.5 ± 1.0% vs. 10.8 ± 0.7%, respectively, N = 24, P < 0.05) and MMP-2 and MMP-9 secretion. Cortical fibroblast secretion of IGF-I binding protein-3 (IGFBP-3), which in turn modulates the autocrine and paracrine actions of IGF-I, was enhanced in the presence of PTC-CM compared with control (1162.2 ± 94.2 vs. 969.1 ± 58.9 ng/mg protein/day, P < 0.05), but no change was observed in cortical fibroblast secretion of IGFBP-2 (260.9 ± 38.8 vs. 290.9 ± 36.6 ng/mg protein/day, P = NS) or IGF-I (56.7 ± 6.6 vs. 57.0 ± 6.8 ng/mg protein/day, P = NS). Human PTC secreted transforming growth factor-β1 (TGF-β1 ) and the AB heterodimer of platelet-derived growth factor (PDGF-AB) in a time-dependent fashion and the augmentation of cortical fibroblasts mitogenesis, collagen...
- Subjects
KIDNEY tubules; FIBROBLASTS; PLATELET-derived growth factor
- Publication
Kidney International, 1998, Vol 54, Issue 3, p747
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1998.00048.x