Thrombin stimulates c-sis gene expression in microvascular endothelial cells

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• Vascular endothelial cells are exposed to various factors at sites of cellular proliferation.
• Platelet-derived growth factor (PDGF) is a key mitogen for perivascular cells.

Purpose of the Study:

• To investigate the regulation of c-sis gene expression and PDGF production in cultured renal microvascular endothelial cells.
• To determine the role of thrombin in this regulation.

Main Methods:

• Cultured renal microvascular endothelial cells were exposed to thrombin.
• c-sis gene message levels were quantified using techniques like Northern blotting (implied).
• PDGF activity in cell media was measured.

Main Results:

• Thrombin exposure increased endothelial cell c-sis message levels 3-5 fold, peaking at 4 hours.
• Thrombin-exposed cells released increased PDGF activity.
• Proteolytically inactive thrombin also stimulated c-sis expression, suggesting a non-proteolytic mechanism.
• Phorbol esters mimicked thrombin's effect, indicating involvement of Protein Kinase C.

Conclusions:

• Thrombin regulates the expression and release of PDGF from endothelial cells in culture.
• Thrombin may stimulate mitogen release in vivo, inducing perivascular cell proliferation.