Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells
Inadequate invasion and excessive apoptosis of trophoblast cells are associated with the development of preeclampsia. Vitamin D deficiency in pregnant women may lead to an increased risk of preeclampsia. However, the underlying mechanisms by which vitamin D is effective in preventing preeclampsia ar...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2023-10-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100676&tlng=en |
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| author | Xiaoyu Tian Lili Zheng Jing Ma Ying Xu Yulin Zhang Yalei Pi |
| author_facet | Xiaoyu Tian Lili Zheng Jing Ma Ying Xu Yulin Zhang Yalei Pi |
| author_sort | Xiaoyu Tian |
| collection | DOAJ |
| description | Inadequate invasion and excessive apoptosis of trophoblast cells are associated with the development of preeclampsia. Vitamin D deficiency in pregnant women may lead to an increased risk of preeclampsia. However, the underlying mechanisms by which vitamin D is effective in preventing preeclampsia are not fully understood. The objectives of this study were to investigate the role of lysosome-associated membrane glycoprotein 3 (LAMP3) in the pathogenesis of preeclampsia and to evaluate whether vitamin D supplementation would protect against the development of preeclampsia by regulating LAMP3 expression. Firstly, the mRNA and protein levels of LAMP3 were significantly upregulated in the placentas of preeclampsia patients compared to normal placentas, especially in trophoblast cells (a key component of the human placenta). In the hypoxia/reoxygenation (H/R)-exposed HTR-8/Svneo trophoblast cells, LAMP3 expression was also upregulated. H/R exposure repressed cell viability and invasion and increased apoptosis of trophoblast cells. siRNA-mediated knockdown of LAMP3 increased cell viability and invasion and suppressed apoptosis of H/R-exposed trophoblast cells. We further found that 1,25(OH)2D3 (the hormonally active form of vitamin D) treatment reduced LAMP3 expression in H/R exposed trophoblast cells. In addition, 1,25(OH)2D3 treatment promoted cell viability and invasion and inhibited apoptosis of H/R-exposed trophoblast cells. Notably, overexpression of LAMP3 abrogated the protective effect of 1,25(OH)2D3 on H/R-exposed trophoblast cells. Collectively, we demonstrated trophoblast cytoprotection by vitamin D, a process mediated via LAMP3. |
| first_indexed | 2024-03-11T16:30:33Z |
| format | Article |
| id | doaj.art-cbcfa9e0357a4b9ea200ee8909844919 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-03-11T16:30:33Z |
| publishDate | 2023-10-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-cbcfa9e0357a4b9ea200ee89098449192023-10-24T07:38:45ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2023-10-015610.1590/1414-431x2023e12816Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cellsXiaoyu Tianhttps://orcid.org/0000-0003-1266-0121Lili Zhenghttps://orcid.org/0000-0003-4540-9267Jing Mahttps://orcid.org/0000-0003-4861-2455Ying Xuhttps://orcid.org/0000-0001-6112-9519Yulin Zhanghttps://orcid.org/0000-0002-0837-2752Yalei Pihttps://orcid.org/0000-0001-5401-6372Inadequate invasion and excessive apoptosis of trophoblast cells are associated with the development of preeclampsia. Vitamin D deficiency in pregnant women may lead to an increased risk of preeclampsia. However, the underlying mechanisms by which vitamin D is effective in preventing preeclampsia are not fully understood. The objectives of this study were to investigate the role of lysosome-associated membrane glycoprotein 3 (LAMP3) in the pathogenesis of preeclampsia and to evaluate whether vitamin D supplementation would protect against the development of preeclampsia by regulating LAMP3 expression. Firstly, the mRNA and protein levels of LAMP3 were significantly upregulated in the placentas of preeclampsia patients compared to normal placentas, especially in trophoblast cells (a key component of the human placenta). In the hypoxia/reoxygenation (H/R)-exposed HTR-8/Svneo trophoblast cells, LAMP3 expression was also upregulated. H/R exposure repressed cell viability and invasion and increased apoptosis of trophoblast cells. siRNA-mediated knockdown of LAMP3 increased cell viability and invasion and suppressed apoptosis of H/R-exposed trophoblast cells. We further found that 1,25(OH)2D3 (the hormonally active form of vitamin D) treatment reduced LAMP3 expression in H/R exposed trophoblast cells. In addition, 1,25(OH)2D3 treatment promoted cell viability and invasion and inhibited apoptosis of H/R-exposed trophoblast cells. Notably, overexpression of LAMP3 abrogated the protective effect of 1,25(OH)2D3 on H/R-exposed trophoblast cells. Collectively, we demonstrated trophoblast cytoprotection by vitamin D, a process mediated via LAMP3.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100676&tlng=enLAMP3Vitamin DTrophoblastInvasionApoptosisPreeclampsia |
| spellingShingle | Xiaoyu Tian Lili Zheng Jing Ma Ying Xu Yulin Zhang Yalei Pi Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells Brazilian Journal of Medical and Biological Research LAMP3 Vitamin D Trophoblast Invasion Apoptosis Preeclampsia |
| title | Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells |
| title_full | Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells |
| title_fullStr | Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells |
| title_full_unstemmed | Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells |
| title_short | Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells |
| title_sort | inhibition of lamp3 mediates the protective effect of vitamin d against hypoxia reoxygenation in trophoblast cells |
| topic | LAMP3 Vitamin D Trophoblast Invasion Apoptosis Preeclampsia |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100676&tlng=en |
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