Connexin43 in post-surgical peritoneal adhesion formation

Objective: Post-surgical peritoneal adhesions are a serious problem for the quality of life and fertility. Yet there are no effective ways of preventing their occurrence. The gap junction protein Cx43 is known to be involved in fibrosis in several different organs and disease conditions often associ...

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Main Authors: Chua, Jia Wang, Thangaveloo, Moogaambikai, Lim, Debbie Xiu En, Madden, Leigh, Phillips, Anthony R. J., Becker, David Lawrence
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/165229
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1652292023-03-26T15:41:49Z Connexin43 in post-surgical peritoneal adhesion formation Chua, Jia Wang Thangaveloo, Moogaambikai Lim, Debbie Xiu En Madden, Leigh Phillips, Anthony R. J. Becker, David Lawrence Lee Kong Chian School of Medicine (LKCMedicine) Skin Research Institute Singapore Science::Medicine Gap Junctions Connexins Objective: Post-surgical peritoneal adhesions are a serious problem for the quality of life and fertility. Yet there are no effective ways of preventing their occurrence. The gap junction protein Cx43 is known to be involved in fibrosis in several different organs and disease conditions often associated with inflammation. Here we examined the Cx43 dynamic expression in an ischemic button model of surgical adhesions. Methods: Using the mouse ischemic button model, Cx43 antisense was delivered in Pluronic gel to attenuate Cx43 expression. The severity of button formation and immunofluorescence analysis of Cx43 and TGF-β1 were performed. The concentration of tissue plasminogen activator via ELISA was also performed. Results: As early as 6 h after button formation, the Cx43 levels were elevated in and around the button and some weak adhesions were formed. By 24 h Cx43 levels had increased further and adhesions were more defined. At 7 days the adhesions were much more robust, opaque, and vascularized, requiring blunt or sharp dissection to break them. Cx43 antisense attenuated its upregulation and, reduced the number and severity of adhesions that formed. Conclusion: Targeting Cx43 after surgical procedures may be a potential therapeutic strategy for preventing adhesion formation or at least reducing their severity. Agency for Science, Technology and Research (A*STAR) Published version This research was funded by Agency for Science, Technology and Research: H17/01/a0/0C9; Agency for Science, Technology and Research: H1701a0004. 2023-03-21T00:53:42Z 2023-03-21T00:53:42Z 2022 Journal Article Chua, J. W., Thangaveloo, M., Lim, D. X. E., Madden, L., Phillips, A. R. J. & Becker, D. L. (2022). Connexin43 in post-surgical peritoneal adhesion formation. Life, 12(11), 1734-. https://dx.doi.org/10.3390/life12111734 2075-1729 https://hdl.handle.net/10356/165229 10.3390/life12111734 36362888 2-s2.0-85141670614 11 12 1734 en H17/01/a0/0C9 H1701a0004 Life © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Gap Junctions
Connexins
spellingShingle Science::Medicine
Gap Junctions
Connexins
Chua, Jia Wang
Thangaveloo, Moogaambikai
Lim, Debbie Xiu En
Madden, Leigh
Phillips, Anthony R. J.
Becker, David Lawrence
Connexin43 in post-surgical peritoneal adhesion formation
description Objective: Post-surgical peritoneal adhesions are a serious problem for the quality of life and fertility. Yet there are no effective ways of preventing their occurrence. The gap junction protein Cx43 is known to be involved in fibrosis in several different organs and disease conditions often associated with inflammation. Here we examined the Cx43 dynamic expression in an ischemic button model of surgical adhesions. Methods: Using the mouse ischemic button model, Cx43 antisense was delivered in Pluronic gel to attenuate Cx43 expression. The severity of button formation and immunofluorescence analysis of Cx43 and TGF-β1 were performed. The concentration of tissue plasminogen activator via ELISA was also performed. Results: As early as 6 h after button formation, the Cx43 levels were elevated in and around the button and some weak adhesions were formed. By 24 h Cx43 levels had increased further and adhesions were more defined. At 7 days the adhesions were much more robust, opaque, and vascularized, requiring blunt or sharp dissection to break them. Cx43 antisense attenuated its upregulation and, reduced the number and severity of adhesions that formed. Conclusion: Targeting Cx43 after surgical procedures may be a potential therapeutic strategy for preventing adhesion formation or at least reducing their severity.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Chua, Jia Wang
Thangaveloo, Moogaambikai
Lim, Debbie Xiu En
Madden, Leigh
Phillips, Anthony R. J.
Becker, David Lawrence
format Article
author Chua, Jia Wang
Thangaveloo, Moogaambikai
Lim, Debbie Xiu En
Madden, Leigh
Phillips, Anthony R. J.
Becker, David Lawrence
author_sort Chua, Jia Wang
title Connexin43 in post-surgical peritoneal adhesion formation
title_short Connexin43 in post-surgical peritoneal adhesion formation
title_full Connexin43 in post-surgical peritoneal adhesion formation
title_fullStr Connexin43 in post-surgical peritoneal adhesion formation
title_full_unstemmed Connexin43 in post-surgical peritoneal adhesion formation
title_sort connexin43 in post-surgical peritoneal adhesion formation
publishDate 2023
url https://hdl.handle.net/10356/165229
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