Evidence map›Paper›PMID 41340077›Full record

ArticleStem cell research & therapy2025

Cx43 hemichannel-mediated paracrine involves in the promotion of MSCs on skin wound healing.

Xiangya Dou, Yaping Zhang, Xuezhou Yang, Yinbo Niu, Dong-En Wang, Huiyun Xu

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Xiangya DouSchool of Life Sciences, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University, Xi'an, China.
Yaping ZhangSchool of Life Sciences, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University, Xi'an, China.
Xuezhou YangSchool of Life Sciences, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University, Xi'an, China.
Yinbo NiuSchool of Life Sciences, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University, Xi'an, China.
Dong-En WangSchool of Life Sciences, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University, Xi'an, China. wde2017@nwpu.edu.cn.
Huiyun XuSchool of Life Sciences, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University, Xi'an, China. celldon@nwpu.edu.cn.

Funding

the National Natural Science Foundation of China 32371240the National Natural Science Foundation of China 32471510
6 · The paper itself

Abstract

backgroundMesenchymal stem cells (MSCs) exhibit therapeutic potential in wound healing, primarily through their paracrine effects. However, the specific mechanisms underlying these effects remain ambiguous. Connexin 43 (Cx43), the most abundantly expressed connexins in MSCs, forms hemichannels that mediate the paracrine release of small molecules, suggesting a potential role in MSC-mediated wound healing.

methodsA full-thickness skin wound model was established in mice to investigate the role of Cx43 hemichannels in MSC-mediated wound healing. Wounds were treated with MSC-conditioned medium (MSC CM), Cx43 hemichannel-inhibited medium (18α-GA CM), or control medium (CTRL CM, complete medium). The assessment of wound healing was conducted through histological and immunofluorescence analyses. Besides, macrophages, endothelial cells, and fibroblasts treated with the three media were subjected to in vitro investigations. The underlying mechanisms were investigated using qRT-PCR, Western blotting, and immunofluorescence.

resultsMSC CM promoted wound healing partly through Cx43-dependent mechanisms. Cx43 hemichannel-dependent ATP release activated purinergic receptors and the AKT signaling pathway to facilitate macrophage polarization during the inflammatory phase of wound healing. Inhibition of Cx43 hemichannels prevented MSC CM-induced angiogenesis activation and fibroblast migration during the proliferation phase.

conclusionsOur findings reveal a novel mechanism that MSCs promote wound healing through Cx43 hemichannel-mediated paracrine, mainly ATP secretion. MSC CM facilitates macrophage polarization, angiogenesis, and fibroblast migration, ultimately enhancing tissue repair. Our finding identifies a novel role for Cx43 hemichannels in the process that MSCs facilitate tissue repair and offer a promising therapeutic strategy in clinical applications to improve wound healing.

Indexed as

Connexin 43Mesenchymal Stem CellsParacrine CommunicationSkinWound HealingAnimalsCulture Media, ConditionedFibroblastsHumansMacrophagesMaleMiceMice, Inbred C57BLConnexin 43Culture Media, Conditioned18α-glycyrrhetinic acidConnexin 43 hemichannelsMacrophage polarizationMesenchymal stem cellsParacrine signalingWound healing

Identifiers

PMID41340077
PMCPMC12676879

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.