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|Title:||Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane||Authors:||Barrett, David W.
John, Rebecca K.
Deprest, Jan A.
Becker, David Lawrence
David, Anna L.
Chowdhury, Tina T.
|Issue Date:||2019||Source:||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||Series/Report no.:||Scientific Reports||Abstract:||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.||URI:||https://hdl.handle.net/10356/106493
|DOI:||10.1038/s41598-019-42379-4||Rights:||© 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/.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
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