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Pentoxifylline Reduces in vitro Renal Myofibroblast Proliferation and Collagen Secretion
- Source :
- American Journal of Nephrology. 20:82-88
- Publication Year :
- 2000
- Publisher :
- S. Karger AG, 2000.
-
Abstract
- Interstitial myofibroblasts (MF) are cells with features of both smooth muscle cells and fibroblasts. They have been universally recognized in situations of tubulointerstitial injury, where their presence has been shown to be a marker of disease progression. The objective of this study was to determine if functions of MF relevant to fibrogenesis can be modified in vitro by the phosphodiesterase inhibitor pentoxifylline (PTX). MF were obtained from sub-culture of normal rat kidney explant outgrowths maintained in DMEM + 20% fetal calf serum (FCS), supplemented with antibiotics. Cells were characterized on the basis of growth characteristics and immunohistochemistry. MF constituted >95% of cells at passage 3. Cell culture media was supplemented with the potential antagonist PTX alone (0, 1, 10, 100 μg/ml) and in combination with TGFβ1 (5 ng/ml). Population kinetics, proliferation and collagen production were determined from cell growth, [3H]thymidine incorporation and [3H]proline incorporation in collagenous proteins, respectively. Both serum-stimulated population growth and proliferation were reduced in a linear fashion by 1, 10 and 100 μg/ml PTX (all p < 0.05 versus 0 μg/ml). Effect of PTX on cell population growth was however reversible when PTX was removed. Basal collagen secretion was decreased by PTX at 10 and 100 μg/ml (p < 0.05 versus 0 μg/ml), although cell layer collagen remained unchanged. Collagen production (secreted and cell layer) was augmented by 5 ng/ml TGFβ1. These effects on collagen production were partially reduced when 100 μg/ml PTX was added. The authors conclude that myofibroblast function can be altered with agonists/antagonists. Attempts to down-regulate fibrogenic functions of MF may therefore offer a valuable therapeutic strategy.
- Subjects :
- medicine.medical_specialty
Phosphodiesterase Inhibitors
In Vitro Techniques
Biology
Kidney
Pentoxifylline
Rats, Sprague-Dawley
Internal medicine
medicine
Animals
Cells, Cultured
Dose-Response Relationship, Drug
Cell growth
Muscle, Smooth
Transforming growth factor beta
Fibroblasts
In vitro
Rats
medicine.anatomical_structure
Endocrinology
Nephrology
Cell culture
biology.protein
Collagen
Myofibroblast
Cell Division
medicine.drug
Explant culture
Subjects
Details
- ISSN :
- 14219670 and 02508095
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- American Journal of Nephrology
- Accession number :
- edsair.doi.dedup.....fd7cfb94afadcd3abbd4e0ca53b83631