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Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation
Proper placentation in the first trimester is essential for a healthy pregnancy in humans. A recent proteomics study of human placental tissue has identified that tripeptidyl peptidase 1 (TPP1) production is reduced in the placenta in early-onset preeclampsia compared to uncomplicated pregnancy. How...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485709/ https://www.ncbi.nlm.nih.gov/pubmed/36147632 http://dx.doi.org/10.1155/2022/6856768 |
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author | Zhou, Wei Dimitriadis, Evdokia |
author_facet | Zhou, Wei Dimitriadis, Evdokia |
author_sort | Zhou, Wei |
collection | PubMed |
description | Proper placentation in the first trimester is essential for a healthy pregnancy in humans. A recent proteomics study of human placental tissue has identified that tripeptidyl peptidase 1 (TPP1) production is reduced in the placenta in early-onset preeclampsia compared to uncomplicated pregnancy. However, it remains to be investigated if TPP1 plays a role in regulating trophoblast cell function during early pregnancy. In this study, immunohistochemistry was used to determine the production and localization of TPP1 in human placenta throughout gestation and the first-trimester decidua/implantation sites. TPP1 siRNA (20 nM) was transfected into a human trophoblast cell line (HTR8/SVneo) to knock down TPP1, and functional consequences on cell adhesion, proliferation, migration, and invasion were analyzed via xCELLigence real-time monitoring. The expression of TPP1 downstream targets was examined by qPCR. Our data show that TPP1 localized to the discrete foci in the cytoplasm in syncytiotrophoblast, cytotrophoblast, and decidual cells across all trimesters of pregnancy. In the first-trimester human decidua, TPP1 exhibited similar staining patterns in the cytotrophoblast cells based at the cell columns. However, minimal/no staining was identified in the HLA-G positive extravillous trophoblast cells (EVTs), especially in the EVTs that invaded in the decidua. Knockdown of TPP1 in HTR8/SVneo cells by 95% significantly impaired cell adhesion and proliferation without affecting cell migration and invasion. qPCR revealed that the expression of cell proliferation markers P21 and MKI67 and TPP1-related genes MRE11, CLN3, and CLN8 was significantly changed after TPP1 knockdown in HTR8/SVneo cells compared to control. Overall, our data demonstrate that TPP1 alters trophoblast cell line function suggesting that it may be involved in regulating human placentation in the first trimester via controlling trophoblast cell adhesion and proliferation. |
format | Online Article Text |
id | pubmed-9485709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-94857092022-09-21 Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation Zhou, Wei Dimitriadis, Evdokia Biomed Res Int Research Article Proper placentation in the first trimester is essential for a healthy pregnancy in humans. A recent proteomics study of human placental tissue has identified that tripeptidyl peptidase 1 (TPP1) production is reduced in the placenta in early-onset preeclampsia compared to uncomplicated pregnancy. However, it remains to be investigated if TPP1 plays a role in regulating trophoblast cell function during early pregnancy. In this study, immunohistochemistry was used to determine the production and localization of TPP1 in human placenta throughout gestation and the first-trimester decidua/implantation sites. TPP1 siRNA (20 nM) was transfected into a human trophoblast cell line (HTR8/SVneo) to knock down TPP1, and functional consequences on cell adhesion, proliferation, migration, and invasion were analyzed via xCELLigence real-time monitoring. The expression of TPP1 downstream targets was examined by qPCR. Our data show that TPP1 localized to the discrete foci in the cytoplasm in syncytiotrophoblast, cytotrophoblast, and decidual cells across all trimesters of pregnancy. In the first-trimester human decidua, TPP1 exhibited similar staining patterns in the cytotrophoblast cells based at the cell columns. However, minimal/no staining was identified in the HLA-G positive extravillous trophoblast cells (EVTs), especially in the EVTs that invaded in the decidua. Knockdown of TPP1 in HTR8/SVneo cells by 95% significantly impaired cell adhesion and proliferation without affecting cell migration and invasion. qPCR revealed that the expression of cell proliferation markers P21 and MKI67 and TPP1-related genes MRE11, CLN3, and CLN8 was significantly changed after TPP1 knockdown in HTR8/SVneo cells compared to control. Overall, our data demonstrate that TPP1 alters trophoblast cell line function suggesting that it may be involved in regulating human placentation in the first trimester via controlling trophoblast cell adhesion and proliferation. Hindawi 2022-09-12 /pmc/articles/PMC9485709/ /pubmed/36147632 http://dx.doi.org/10.1155/2022/6856768 Text en Copyright © 2022 Wei Zhou and Evdokia Dimitriadis. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhou, Wei Dimitriadis, Evdokia Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation |
title | Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation |
title_full | Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation |
title_fullStr | Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation |
title_full_unstemmed | Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation |
title_short | Tripeptidyl Peptidase 1 Regulates Human Trophoblast Cell Proliferation Implying a Role in Placentation |
title_sort | tripeptidyl peptidase 1 regulates human trophoblast cell proliferation implying a role in placentation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485709/ https://www.ncbi.nlm.nih.gov/pubmed/36147632 http://dx.doi.org/10.1155/2022/6856768 |
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