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Cited by 84Connexins and lens biologyAcute Ischemic Stroke ManagementBarrier Structure and Function Studies

The multifaceted role of astrocyte connexin 43 in ischemic stroke through forming hemichannels and gap junctions

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Liang, Zhen, Wang, Xu, Hao, Yulei, Qiu, Lin, Lou, Yingyue, Zhang, Yaoting, Ma, Di, Feng, Jiachun·2020·Frontiers in Neurology
DOI 10.3389/fneur.2020.00703PMC PMC7411525
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Abstract

Ischemic stroke is a multi-factorial cerebrovascular disease with high worldwide morbidity and mortality. In the past few years, multiple studies have revealed the underlying mechanism of ischemia/reperfusion injury, including calcium overload, amino acid toxicity, oxidative stress, and inflammation. Connexin 43 (Cx43), the predominant connexin protein in astrocytes, has been recently proven to display non-substitutable roles in the pathology of ischemic stroke development and progression through forming gap junctions and hemichannels. Under normal conditions, astrocytic Cx43 could be found in hemichannels or in the coupling with other hemichannels on astrocytes, neurons, or oligodendrocytes to form the neuro-glial syncytium, which is involved in metabolites exchange between communicated cells, thus maintaining the homeostasis of the CNS environment. In ischemic stroke, the phosphorylation of Cx43 might cause the degradation of gap junctions and the opening of hemichannels, contributing to the release of inflammatory mediators. However, the remaining gap junctions could facilitate the exchange of protective and harmful metabolites between healthy and injured cells, protecting the injured cells to some extent or damaging the healthy cells depending on the balance of the exchange of protective and harmful metabolites. In this study, we review the changes in astrocytic Cx43 expression and distribution as well as the influence of these changes on the function of astrocytes and other cells in the CNS, providing new insight into the pathology of ischemic stroke injury; we also discuss the potential of astrocytic Cx43 as a target for the treatment of ischemic stroke.

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  • iAstrocytes drastically changed morphology from day 30 (with FCS) to day 44 (without FCS), and show increased membrane incorporation of gap junction protein GJA1, which is an indication of mature, adult astrocytes.

    “Our iAstrocytes drastically changed morphology from day 30 (with FCS) to day 44 (without FCS), and show an increased membrane incorporation of gap junction protein GJA1, which is an indication of mature, adult astrocytes (Liang et al., 2020).”

    From APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes (2022) · cites this paper as Liang et al., 2020

    The ‘Structure and Distribution of Cx43’ section identifies Cx43 as a major gap-junction protein in astrocytes and describes its presence on astrocytic membranes in the adult mammalian brain. It does not say that increased membrane incorporation indicates astrocyte maturity. The day-30-to-day-44 observations are the citing authors’ own findings, not findings attributed to Liang et al. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Liang, Z., Wang, X., Hao, Y., Qiu, L., Lou, Y., Zhang, Y., Ma, D., & Feng, J.
Affiliations
First Hospital of Jilin University (CN)
Corresponding author
  • Ma, Di
  • Feng, Jiachun
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2020-07-31
Volume
11
Pages
703-703
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2020.00703
PMC
PMC7411525
OpenAlex
W3046832479
Cited by
84
References
2
Citations by year
2026: 9 · 2025: 17 · 2024: 15 · 2023: 18 · 2022: 17 · 2021: 8
FWCI
1.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
connexin 43, astrocytes, ischemic stroke, hemichannels, gap junctions, ischemia-reperfusion injury, Cx43 phosphorylation, inflammatory mediators, oxidative stress, calcium overload

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