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Effects of PDGF on inositol phosphates, Ca2+, and contraction of mesangial cells
Abstract:
Platelet-derived growth factor (PDGF) is a potent mitogen and vasoactive polypeptide for aortic smooth muscle. Because contractile glomerular mesangial cells synthesize a PDGF-like molecule and may respond to PDGF released by infiltrating cells at the site of glomerular inflammation, we studied the effects of exogenous, highly purified PDGF on 1) contraction of cultured rat mesangial cells and 2) membrane phosphoinositide turnover and cytosolic free calcium ([Ca2+]i), as putative mechanisms of membrane signal transduction. PDGF, 10(-11) and 10(-10) M, contracted 56.1 +/- 5.2 and 72.9 +/- 6.4% of the cells, respectively, with an average decrease of cross-sectional area of 22.0 +/- 2.6 and 28.1 +/- 2.7% of basal, as assessed by image-analysis microscopy. PDGF also rapidly increased total water-soluble inositol phosphates, measured after anion-exchange chromatography on perchloric acid-extracted cells, and simultaneously raised [Ca2+]i, measured by the fluorescent intracellular probe fura-2, from basal levels of 83.1 +/- 6.8 to a peak of 229.4 +/- 20.0 nM. We conclude that PDGF stimulates contraction of rat mesangial cells via a phospholipase C-dependent pathway, with potential relevance to the control of glomerular hemodynamics and mesangial proliferation in immune-mediated glomerular disease.
Insights
Platelet-derived growth factor (PDGF) triggers rat mesangial cell contraction and alters intracellular calcium levels. This suggests PDGF influences glomerular hemodynamics and proliferation in inflammatory kidney diseases.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Platelet-derived growth factor (PDGF) is a known mitogen and vasoactive polypeptide.
- Glomerular mesangial cells synthesize a PDGF-like molecule and may respond to external PDGF during inflammation.
Purpose of the Study:
- To investigate the effects of exogenous PDGF on cultured rat mesangial cell contraction.
- To examine PDGF's impact on membrane phosphoinositide turnover and cytosolic free calcium ([Ca2+]i) as signal transduction mechanisms.
Main Methods:
- Cultured rat mesangial cells were treated with varying concentrations of purified PDGF.
- Cell contraction was assessed using image-analysis microscopy.
- Changes in inositol phosphates and cytosolic free calcium ([Ca2+]i) were measured using anion-exchange chromatography and fura-2 fluorescence, respectively.
Main Results:
- PDGF induced significant contraction in mesangial cells in a dose-dependent manner.
- PDGF rapidly increased total water-soluble inositol phosphates.
- PDGF elevated cytosolic free calcium ([Ca2+]i) from basal levels to a peak of 229.4 +/- 20.0 nM.
Conclusions:
- PDGF stimulates mesangial cell contraction through a phospholipase C-dependent pathway.
- These findings suggest PDGF plays a role in regulating glomerular hemodynamics and mesangial cell proliferation in immune-mediated glomerular diseases.