Function of caspase-14 in trophoblast differentiation

Background: Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast di...

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Main Authors: White, L., Declercq, W., Arfuso, Frank, Charles, A., Dharmarajan, Arunasalam
Format: Journal Article
Published: 2009
Online Access:http://hdl.handle.net/20.500.11937/42732
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author White, L.
Declercq, W.
Arfuso, Frank
Charles, A.
Dharmarajan, Arunasalam
author_facet White, L.
Declercq, W.
Arfuso, Frank
Charles, A.
Dharmarajan, Arunasalam
author_sort White, L.
building Curtin Institutional Repository
collection Online Access
description Background: Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. Methods: Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. Results: Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. Conclusion: Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease. © 2009 White et al; licensee BioMed Central Ltd.
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spelling curtin-20.500.11937-427322017-09-13T15:05:24Z Function of caspase-14 in trophoblast differentiation White, L. Declercq, W. Arfuso, Frank Charles, A. Dharmarajan, Arunasalam Background: Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. Methods: Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. Results: Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. Conclusion: Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease. © 2009 White et al; licensee BioMed Central Ltd. 2009 Journal Article http://hdl.handle.net/20.500.11937/42732 10.1186/1477-7827-7-98 unknown
spellingShingle White, L.
Declercq, W.
Arfuso, Frank
Charles, A.
Dharmarajan, Arunasalam
Function of caspase-14 in trophoblast differentiation
title Function of caspase-14 in trophoblast differentiation
title_full Function of caspase-14 in trophoblast differentiation
title_fullStr Function of caspase-14 in trophoblast differentiation
title_full_unstemmed Function of caspase-14 in trophoblast differentiation
title_short Function of caspase-14 in trophoblast differentiation
title_sort function of caspase-14 in trophoblast differentiation
url http://hdl.handle.net/20.500.11937/42732