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Transforming growth factor-beta: signal transduction via protein kinase C in cultured embryonic vascular smooth
R W Wrenn1, C L Raeuber, L E Herman
1Department of Cellular Biology and Anatomy, School of Medicine, Medical College of Georgia, Augusta 30912.
Abstract:
Transforming growth factor-beta (TGF-beta), an ubiquitous regulatory peptide, has diverse effects on the differentiation and behavior of vascular smooth muscle cells (VSMC). However, the molecular mechanism through which TGF-alpha exerts its effects remains obscure. We investigated the phosphoinositide/protein kinase C [PKC] signaling pathway in the action of TGF-beta on cultured embryonic avian VSMC of differing lineage: a) thoracic aorta, derived from the neural crest; and b) abdominal aorta, derived from mesenchyme. The second messenger responsible for activation of PKC is sn-1,2-diacylglycerol [DAG]; TGF-beta increased the mass amounts of DAG in the membranes of neural crest-derived VSMC concurrent with translocation of PKC from the soluble to the membrane fraction, but TGF-beta had no effect on the DAG or PKC of mesenchyme-derived VSMC. TGF-beta potentiated the growth of platelet-derived growth factor (PDGF)-treated, neural crest-derived VSMC; but abolished PDGF-induced growth of mesenchymal cells. It is concluded that molecular and functional responses of VSMC to TGF-beta are heterogeneous and are functions of the embryonic lineage of the VSMC.
Insights
Transforming growth factor-beta (TGF-beta) triggers distinct vascular smooth muscle cell (VSMC) responses based on embryonic origin. Neural crest-derived VSMC activate protein kinase C (PKC) signaling, unlike mesenchymal cells, influencing cell growth.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Transforming growth factor-beta (TGF-beta) is a key regulator of vascular smooth muscle cell (VSMC) differentiation and behavior.
- The precise molecular mechanisms underlying TGF-beta's actions on VSMC remain incompletely understood.
- VSMC heterogeneity in response to growth factors is increasingly recognized.
Purpose of the Study:
- To investigate the role of the phosphoinositide/protein kinase C (PKC) signaling pathway in mediating TGF-beta effects on VSMC.
- To compare TGF-beta's impact on VSMC derived from different embryonic lineages (neural crest vs. mesenchyme).
Main Methods:
- Cultured embryonic avian VSMC from thoracic (neural crest-derived) and abdominal (mesenchyme-derived) aortas were utilized.
- Levels of sn-1,2-diacylglycerol (DAG) and translocation of PKC were measured following TGF-beta treatment.
- The effect of TGF-beta on platelet-derived growth factor (PDGF)-induced VSMC proliferation was assessed.
Main Results:
- TGF-beta increased DAG mass and induced PKC translocation in neural crest-derived VSMC, but not in mesenchyme-derived VSMC.
- TGF-beta potentiated PDGF-induced growth in neural crest-derived VSMC.
- TGF-beta inhibited PDGF-induced growth in mesenchyme-derived VSMC.
Conclusions:
- VSMC exhibit heterogeneous molecular and functional responses to TGF-beta.
- These differential responses are dependent on the embryonic lineage of the VSMC.
- The PKC signaling pathway mediates TGF-beta's lineage-specific effects on VSMC growth and behavior.