Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 28;13(1):3.
doi: 10.21037/atm-24-158. Epub 2025 Feb 25.

Connexin 43 expression in irradiated human neck skin: a prospective case-control study

Hao Li  1 , Jacob William Wilson  2 , Jocelin Wei Ling Poh  3 , Leigh Edward Madden  2 , Timothy Cheo  4 , Francis Cho Hao Ho  4 , Ming Yann Lim  1 , Yoko Wong  5 , David Lawrence Becker  2   6
Affiliations

Connexin 43 expression in irradiated human neck skin: a prospective case-control study

Hao Li et al. Ann Transl Med. .

Abstract

Background: Overexpression of connexin 43 (Cx43) is seen in chronic cutaneous wounds of humans, and downregulation of Cx43 expedites healing. Human epithelia that have received radiotherapy can also suffer from chronic wounds. Since increased expression of Cx43 was observed in murine skin following irradiation, we sought to confirm this in irradiated human neck skin because Cx43 inhibition may be a novel treatment of wounds in such tissue.

Methods: We prospectively recruited adult patients who underwent elective neck surgery between November 2017 and March 2018 in the Otorhinolaryngology Department of a tertiary hospital in Singapore. A sample size of five patients with prior radiotherapy to 25 controls without radiotherapy was planned a priori. Immunohistochemical staining of Cx43 was performed in the neck skin obtained from the patients and quantified under confocal microscopy. The association between demographic factors, comorbidities of the patients, and Cx43 expression was explored. Wound healing was assessed between 7 to 14 days postoperatively.

Results: Five patients received radiotherapy 9 months to 27 years before surgery. The expression of Cx43 was 94.2 vs. 146.4 pixel-area/nucleus in the epidermis with or without radiotherapy, respectively (P=0.39). The demographics and co-morbidities of the patients with or without radiotherapy were similar except for relative anemia in the patients who had radiotherapy (hemoglobin of 12.15 vs. 14.10 g/dL, P=0.02), but hemoglobin was not correlated with Cx43 expression (P=0.93). All skin incisions healed without dehiscence.

Conclusions: Previous radiotherapy may not alter Cx43 expression in human neck skin. Whether the same is true for chronic radiation-induced wounds or acute radiation-induced dermatitis should be investigated.

Keywords: Connexin 43 (Cx43); human skin; neck; overexpression; radiation.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-24-158/coif). H.L. reports that this work was supported by the National Medical Research Council of Singapore (research grant for Master of Clinical Investigation, National University of Singapore). The funding agency did not participate in the study in any other way. D.L.B. is the founding scientist of CoDa Therapeutics, a company that produces anti-sense oligonucleotide against connexin 43, but he and his laboratory members were blinded to the radiation status of the samples in this study. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Distribution of Cx43 expression in adult neck skin with or without previous radiotherapy. Cx43, connexin 43.
Figure 3
Figure 3
Images of Cx43 expression in the epidermis of human neck skin. (A) Low expression level of 21.1 pixel-area/nucleus. (B) High expression level of 447.4 pixel-area/nucleus. The magnification was 40 times (40×). Cx43 stains green; nuclei stain blue. Cx43, connexin 43.
See this image and copyright information in PMC

References

    1. Coutinho P, Qiu C, Frank S, et al. Dynamic changes in connexin expression correlate with key events in the wound healing process. Cell Biol Int 2003;27:525-41. 10.1016/s1065-6995(03)00077-5 - DOI - PubMed
    1. Qiu C, Coutinho P, Frank S, et al. Targeting connexin43 expression accelerates the rate of wound repair. Curr Biol 2003;13:1697-703. 10.1016/j.cub.2003.09.007 - DOI - PubMed
    1. Davis NG, Phillips A, Becker DL. Connexin dynamics in the privileged wound healing of the buccal mucosa. Wound Repair Regen 2013;21:571-8. 10.1111/wrr.12054 - DOI - PubMed
    1. Tarzemany R, Jiang G, Larjava H, et al. Expression and function of connexin 43 in human gingival wound healing and fibroblasts. PLoS One 2015;10:e0115524. 10.1371/journal.pone.0115524 - DOI - PMC - PubMed
    1. Mendoza-Naranjo A, Cormie P, Serrano AE, et al. Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg ulcers, influences migration, adhesion and activation of Rho GTPases. PLoS One 2012;7:e37374. 10.1371/journal.pone.0037374 - DOI - PMC - PubMed

LinkOut - more resources