Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane
Mechanical and inflammatory signals in the fetal membrane play an important role in extracellular matrix (ECM) remodelling in order to dictate the timing of birth. We developed a mechanical model that mimics repetitive stretching of the amniotic membrane (AM) isolated from regions over the placenta...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/106493 http://hdl.handle.net/10220/48950 |
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| author | Barrett, David W. John, Rebecca K. Thrasivoulou, Christopher Mata, Alvaro Deprest, Jan A. Becker, David Lawrence David, Anna L. Chowdhury, Tina T. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Barrett, David W. John, Rebecca K. Thrasivoulou, Christopher Mata, Alvaro Deprest, Jan A. Becker, David Lawrence David, Anna L. Chowdhury, Tina T. |
| author_sort | Barrett, David W. |
| collection | NTU |
| description | Mechanical and inflammatory signals in the fetal membrane play an important role in extracellular matrix (ECM) remodelling in order to dictate the timing of birth. We developed a mechanical model that mimics repetitive stretching of the amniotic membrane (AM) isolated from regions over the placenta (PAM) or cervix (CAM) and examined the effect of cyclic tensile strain (CTS) on mediators involved in mechanotransduction (Cx43, AKT), tissue remodelling (GAGs, elastin, collagen) and inflammation (PGE2, MMPs). In CAM and PAM specimens, the application of CTS increased GAG synthesis, PGE2 release and MMP activity, with concomitant reduction in collagen and elastin content. Co-stimulation with CTS and pharmacological agents that inhibit either Cx43 or AKT, differentially influenced collagen, GAG and elastin in a tissue-dependent manner. SHG confocal imaging of collagen fibres revealed a reduction in SHG intensity after CTS, with regions of disorganisation dependent on tissue location. CTS increased Cx43 and AKT protein and gene expression and the response could be reversed with either CTS, the Cx43 antisense or AKT inhibitor. We demonstrate that targeting Cx43 and AKT prevents strain-induced ECM damage and promotes tissue remodelling mechanisms in the AM. We speculate that a combination of inflammatory and mechanical factors could perturb typical mechanotransduction processes mediated by Cx43 signalling. Cx43 could therefore be a potential therapeutic target to prevent inflammation and preterm premature rupture of the fetal membranes. |
| first_indexed | 2024-10-01T06:40:30Z |
| format | Journal Article |
| id | ntu-10356/106493 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:40:30Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1064932021-03-10T02:51:42Z Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane Barrett, David W. John, Rebecca K. Thrasivoulou, Christopher Mata, Alvaro Deprest, Jan A. Becker, David Lawrence David, Anna L. Chowdhury, Tina T. Lee Kong Chian School of Medicine (LKCMedicine) Biomedical Engineering Paediatric Research DRNTU::Science::Medicine Mechanical and inflammatory signals in the fetal membrane play an important role in extracellular matrix (ECM) remodelling in order to dictate the timing of birth. We developed a mechanical model that mimics repetitive stretching of the amniotic membrane (AM) isolated from regions over the placenta (PAM) or cervix (CAM) and examined the effect of cyclic tensile strain (CTS) on mediators involved in mechanotransduction (Cx43, AKT), tissue remodelling (GAGs, elastin, collagen) and inflammation (PGE2, MMPs). In CAM and PAM specimens, the application of CTS increased GAG synthesis, PGE2 release and MMP activity, with concomitant reduction in collagen and elastin content. Co-stimulation with CTS and pharmacological agents that inhibit either Cx43 or AKT, differentially influenced collagen, GAG and elastin in a tissue-dependent manner. SHG confocal imaging of collagen fibres revealed a reduction in SHG intensity after CTS, with regions of disorganisation dependent on tissue location. CTS increased Cx43 and AKT protein and gene expression and the response could be reversed with either CTS, the Cx43 antisense or AKT inhibitor. We demonstrate that targeting Cx43 and AKT prevents strain-induced ECM damage and promotes tissue remodelling mechanisms in the AM. We speculate that a combination of inflammatory and mechanical factors could perturb typical mechanotransduction processes mediated by Cx43 signalling. Cx43 could therefore be a potential therapeutic target to prevent inflammation and preterm premature rupture of the fetal membranes. Published version 2019-06-26T04:54:02Z 2019-12-06T22:12:58Z 2019-06-26T04:54:02Z 2019-12-06T22:12:58Z 2019 Journal Article Barrett, D. W., John, R. K., Thrasivoulou, C., Mata, A., Deprest, J. A., Becker, D. L., . . . Chowdhury, T. T. (2019). Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane. Scientific Reports, 9(1), 6718-. doi:10.1038/s41598-019-42379-4 https://hdl.handle.net/10356/106493 http://hdl.handle.net/10220/48950 10.1038/s41598-019-42379-4 en Scientific Reports © 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 11 p. application/pdf |
| spellingShingle | Biomedical Engineering Paediatric Research DRNTU::Science::Medicine Barrett, David W. John, Rebecca K. Thrasivoulou, Christopher Mata, Alvaro Deprest, Jan A. Becker, David Lawrence David, Anna L. Chowdhury, Tina T. Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane |
| title | Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane |
| title_full | Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane |
| title_fullStr | Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane |
| title_full_unstemmed | Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane |
| title_short | Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane |
| title_sort | targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane |
| topic | Biomedical Engineering Paediatric Research DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/106493 http://hdl.handle.net/10220/48950 |
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