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Biological responses to PDGF-BB versus PDGF-DD in human mesangial cells
C R C van Roeyen1, T Ostendorf, B Denecke
1Division of Nephrology, RWTH Aachen University, Aachen, Germany.
Kidney International
|March 25, 2006
Summary
Platelet-derived growth factors (PDGF)-BB and PDGF-DD both stimulate human mesangial cell proliferation and activate key signaling pathways. Despite some differences in gene regulation, both PDGF-BB and PDGF-DD ultimately induce similar protein expression, primarily through the PDGF beta-receptor.
Area of Science:
- Cell Biology
- Molecular Biology
- Renal Physiology
Background:
- Platelet-derived growth factor (PDGF)-BB and PDGF-DD are implicated in mesangial cell proliferation.
- PDGF-BB binds to both PDGF alpha- and beta-receptors, while PDGF-DD shows selectivity for the beta-receptor.
- Understanding their distinct and overlapping signaling roles is crucial for renal biology.
Purpose of the Study:
- To compare the signal transduction and gene expression induced by PDGF-BB and PDGF-DD in primary human mesangial cells (HMCs).
- To investigate potential differences in biological activities mediated by PDGF-BB and PDGF-DD.
- To elucidate the receptor usage and downstream pathways involved in PDGF-induced HMC responses.
Main Methods:
- Primary human mesangial cells (HMCs) were treated with PDGF-BB and PDGF-DD.
- Signal transduction pathways, including extracellular signal-regulated kinase (ERK) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT), were analyzed.
- Gene expression profiling using gene chip arrays and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed.
- Protein expression levels of matrix metalloproteinases (MMPs) were assessed.
Main Results:
- Both PDGF-BB and PDGF-DD induced phosphorylation and activation of ERK1/2, STAT1, and STAT3 in HMCs.
- HMC proliferation stimulated by either PDGF-BB or PDGF-DD was inhibited by specific pathway inhibitors (MAPK, JAK/STAT, PI3K).
- PDGF-BB uniquely regulated MMP-13 and MMP-14 gene expression, while PDGF-DD did not show exclusive gene regulation.
- At the protein level, both PDGF-BB and PDGF-DD equally induced MMP-13 and MMP-14.
Conclusions:
- PDGF-BB and PDGF-DD elicit similar biological responses in HMCs, though potentially at different potencies.
- Apparent differential gene regulation by PDGF-BB and PDGF-DD did not translate to distinct protein expression.
- In HMCs, both PDGF-BB and PDGF-DD primarily exert their biological effects through the PDGF beta-receptor.
