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TGF-beta stimulates rat mesangial cell proliferation in culture: role of PDGF beta-receptor expression
U Haberstroh1, G Zahner, M Disser
1Department of Medicine, University of Frankfurt, Federal Republic of Germany.
Abstract:
Transforming growth factor (TGF)-beta is known to increase mesangial cell (MC) matrix; however, its possible role on MC proliferation is controversial. We therefore studied the influence of TGF-beta on MC proliferation in culture and evaluated its effect on the platelet-derived growth factor (PDGF) B-chain as well as the expression of the PDGF beta-receptor. TGF-beta (1 ng/ml) increases MC DNA synthesis by approximately threefold after 48 h of incubation. TGF-beta-induced MC proliferation was also confirmed by cell counts. A neutralizing anti-TGF-beta antibody completely blocked this growth promoting activity. The levels of PDGF beta-receptor steady-state mRNA were increased by TGF-beta at 48 h. This was associated with an increase in receptor density per cell as measured by receptor kinetic studies. PDGF B-chain mRNA was also increased by TGF-beta at 48 h. A neutralizing anti-PDGF B-antibody causes no reduction of TGF-beta-induced DNA synthesis; however, suramin completely inhibited the mitogenic effect of TGF-beta. We conclude that TGF-beta stimulates MC growth in long-term culture, a process in which upregulation of the PDGF beta-receptor and enhanced synthesis of PDGF B-chain might be involved.
Insights
Transforming growth factor-beta (TGF-beta) significantly increases mesangial cell (MC) proliferation in culture. This growth stimulation involves upregulation of the platelet-derived growth factor (PDGF) beta-receptor and PDGF B-chain synthesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Renal Physiology
Background:
- Transforming growth factor-beta (TGF-beta) is implicated in extracellular matrix production in mesangial cells (MCs).
- The role of TGF-beta in MC proliferation remains controversial, necessitating further investigation.
Purpose of the Study:
- To investigate the effect of TGF-beta on MC proliferation in vitro.
- To evaluate TGF-beta's influence on platelet-derived growth factor (PDGF) B-chain and PDGF beta-receptor expression in MCs.
Main Methods:
- Mesangial cells were cultured and treated with TGF-beta.
- Cell proliferation was assessed via DNA synthesis assays and cell counts.
- Expression levels of PDGF B-chain and PDGF beta-receptor mRNA were measured.
- Neutralizing antibodies and suramin were used to block specific pathways.
Main Results:
- TGF-beta (1 ng/ml) increased MC DNA synthesis approximately threefold after 48 hours.
- TGF-beta treatment led to increased PDGF beta-receptor mRNA levels and receptor density.
- PDGF B-chain mRNA levels were also elevated by TGF-beta.
- Anti-TGF-beta antibodies blocked proliferation, while anti-PDGF B-antibodies did not significantly reduce it.
Conclusions:
- TGF-beta stimulates mesangial cell growth in long-term culture.
- Upregulation of the PDGF beta-receptor and enhanced PDGF B-chain synthesis are likely involved in TGF-beta-induced MC proliferation.
- Suramin effectively inhibited the mitogenic effects of TGF-beta on MCs.