ADAM17 regulates TNFα production by placental trophoblasts
R Ma1, Y Gu, L J Groome
1Dept. of Gynecology, The Third Hospital of Harbin Medical University, Harbin, China.
Placenta
|October 25, 2011
Summary
Preeclampsia involves increased placental tumor necrosis factor-alpha (TNFα). This study found elevated ADAM17 expression in preeclamptic placentas, suggesting its role in TNFα production under oxidative stress.
Area of Science:
- Reproductive Biology
- Cellular and Molecular Medicine
- Pathophysiology
Background:
- Preeclampsia is characterized by placental dysfunction, with increased trophoblast tumor necrosis factor-alpha (TNFα) production being a key feature.
- The precise mechanisms driving elevated TNFα in preeclamptic placentas remain largely unelucidated.
- ADAM17, a metallopeptidase, is identified as a critical enzyme for converting TNFα.
Purpose of the Study:
- To investigate the expression of ADAM17 in placentas from normal and preeclamptic pregnancies.
- To determine if hypoxia/oxidative stress modulates ADAM17 expression and subsequent TNFα production in placental trophoblasts.
- To elucidate the role of ADAM17 in TNFα production within placental trophoblasts.
Main Methods:
- Comparative analysis of ADAM17 expression in placentas from normal versus preeclamptic pregnancies.
- In vitro study using isolated trophoblasts treated with cobalt (II) chloride (CoCl(2)) to mimic hypoxia/oxidative stress.
- Assessment of TNFα production, ADAM17 expression, HO-1, and caspase-3 levels following CoCl(2) stimulation.
- Pharmacological inhibition of metallopeptidase activity (GM6001) and genetic silencing of ADAM17 (siRNA) to confirm ADAM17's role.
Main Results:
- ADAM17 expression was significantly increased in placentas from preeclamptic pregnancies compared to normal ones (p < 0.05).
- CoCl(2) treatment induced a dose-dependent increase in TNFα production in trophoblasts, correlating with enhanced ADAM17 expression.
- Hypoxia/oxidative stress also upregulated HO-1 and caspase-3 expression in trophoblasts.
- Inhibition of ADAM17 activity or expression significantly blocked CoCl(2)-induced TNFα production.
Conclusions:
- Increased ADAM17 expression in preeclamptic placentas is observed.
- Hypoxia/oxidative stress can enhance ADAM17 expression and subsequently increase TNFα production in placental trophoblasts.
- ADAM17 plays a crucial role in mediating TNFα production in placental trophoblasts, potentially contributing to placental dysfunction in preeclampsia.
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