Human renal fibroblasts modulate proximal tubule cell growth and transport via the IGF-I axis
| Autor: | Michael Field, Bronwyn K. Brew, Carol A. Pollock, David W. Johnson, Philip Poronnik, Heather J. Saunders, David I. Cook, Akos Z. Gyory, Anand N. Ganesan, Robert C. Baxter |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Kidney Cortex Sodium-Hydrogen Exchangers endocrine system diseases medicine.medical_treatment receptors Cell Communication Biology Binding Competitive Insulin-like growth factor-binding protein Antibodies Receptor IGF Type 1 Kidney Tubules Proximal sodium-hydrogen antiporter Insulin-like growth factor Paracrine signalling Cell–cell interaction Neutralization Tests Internal medicine Paracrine Communication medicine Humans RNA Messenger Insulin-Like Growth Factor I Cells Cultured kidney cortex physiology insulin-like growth factor binding proteins Cell growth Growth factor progressive renal disease Biological Transport Fibroblasts Blotting Northern Peptide Fragments Cell biology Sodium–hydrogen antiporter Insulin-Like Growth Factor Binding Protein 2 Endocrinology Insulin-Like Growth Factor Binding Protein 3 Cell culture Nephrology Culture Media Conditioned biology.protein Cell Division |
| Zdroj: | Kidney International. 52(6):1486-1496 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.1997.479 |
| Popis: | Human renal fibroblasts modulate proximal tubule cell growth and transport via the IGF-I axis. To determine the paracrine interactions involved in the tubulointerstitial response to progressive renal disease, the role of insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) in in vitro interactions between human proximal tubule cells (PTC) and renal cortical fibroblasts (CF) were studied in primary cell culture. PTC growth and transport were increased in the presence of CF-conditioned media (CF-CM), as shown by increased thymidine incorporation, cellular protein content and sodium-hydrogen exchange (NHE) activity, to 185 ± 31% (P < 0.01), 150 ± 18% (P < 0.05) and 195 ± 27% (P < 0.01) of the control values, respectively. IGF-I was produced by cultured CF at a rate of 64.6 ± 7.5 ng/mg protein/day. Exogenous IGF-I applied to PTC provoked similar enhancement of growth and NHE activity as CF-CM and the stimulatory effect of CF-CM was blocked by specific immunoneutralization of IGF-I receptors. These receptors were threefold more abundant on PTC basolateral versus apical membranes. IGF binding proteins (IGFBP)-2 and IGFBP-3 were secreted by CF at rates of 694 ± 88 and 1769 ± 45 ng/mg/day, with the release of IGFBP-3 being enhanced in the presence of PTC-CM (120.0 ± 9.7% of control, P < 0.01). Moreover, the addition of CF-CM to PTC increased cell-associated IGFBP-3 on PTC surfaces, without changes in IGF-I receptor numbers or affinity and without changes in PTC mRNA for IGFBP-3. Des(1-3)IGF-I, an analog that binds to the IGF-I receptor but not to IGFBPs, provided a less potent stimulus for PTC growth compared with IGF-I, indicating that cell-associated IGFBP-3 facilitates the action of IGF-I on PTC. The results support important paracrine roles for both IGF-I and IGFBPs in the interstitial regulation of proximal tubule growth and transport. |
| Databáze: | OpenAIRE |
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