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Induction of angiotensin-converting enzyme by oncostatin m in human endothelial cells
O Saijonmaa1, T Nyman, R Kosonen
1Minerva Institute for Medical Research, Helsinki, Finland. Outi.Saijonmaa@Kruuna.Helsinki.fi
Objective:
To examine the role of oncostatin M (OSM) in the regulation of angiotensin converting enzyme (ACE) in endothelial cells.
Methods:
Cultured endothelial cells were incubated with OSM (25-200 pM) for 24 h. Incubations were performed without or with the tyrosine kinase inhibitor, herbimycin (87 nM), or the selective MAP kinase kinase inhibitor, PD98059 (50 microM). ACE amount in intact endothelial cells was measured by an inhibitor binding assay and ACE mRNA levels by RNase protection assay.
Results:
OSM caused a dose dependent increase in ACE amount and increased the expression of ACE mRNA. The stimulatory effect of OSM was inhibited by pretreatments with herbimycin or PD98059.
Conclusions:
OSM induced ACE in cultured HUVECs. Tyrosine kinase and MAPK activation were probably involved in ACE induction. Local induction of ACE by OSM in the vascular wall may be a consequence of inflammatory processes leading to locally increased production of angiotensin II and breakdown of bradykinin.
Insights
Oncostatin M (OSM) increases angiotensin converting enzyme (ACE) in endothelial cells by activating tyrosine kinase and MAPK pathways. This suggests OSM may contribute to inflammatory processes affecting blood pressure regulation.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Angiotensin converting enzyme (ACE) plays a critical role in blood pressure regulation and the renin-angiotensin system.
- Endothelial cells are key regulators of vascular tone and function.
- Oncostatin M (OSM) is a cytokine implicated in inflammatory processes.
Purpose of the Study:
- To investigate the effect of Oncostatin M (OSM) on the expression and regulation of angiotensin converting enzyme (ACE) in endothelial cells.
- To elucidate the signaling pathways involved in OSM-induced ACE regulation.
Main Methods:
- Primary human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of OSM.
- Inhibitors of tyrosine kinase (herbimycin) and MAP kinase kinase (PD98059) were used to probe signaling pathways.
- ACE protein levels were quantified using an inhibitor binding assay.
- ACE mRNA expression was determined by RNase protection assay.
Main Results:
- OSM significantly increased both ACE protein amount and ACE mRNA levels in a dose-dependent manner.
- The stimulatory effect of OSM on ACE was significantly attenuated by pretreatment with herbimycin or PD98059.
- These findings indicate that tyrosine kinase and MAP kinase pathways are involved in OSM-mediated ACE induction.
Conclusions:
- Oncostatin M induces ACE expression in cultured human umbilical vein endothelial cells (HUVECs).
- The induction of ACE by OSM likely involves the activation of tyrosine kinase and mitogen-activated protein kinase (MAPK) signaling cascades.
- Local ACE induction by OSM in the vascular wall could be linked to inflammatory conditions, potentially influencing local angiotensin II production and bradykinin breakdown.