Reduction of connexin43 in human endothelial progenitor cells impairs the angiogenic potential

Wang, Hsueh-Hsiao; Su, Cheng‐Huang; Wu, Yih‐Jer; Li, Jiun-Yi; Tseng, Ya-Ming; Lin, Yi‐Chun; Hsieh, Chin-Ling; Tsai, Cheng‐Ho; Yeh, Hung‐I

doi:10.1007/s10456-013-9335-z

Cited by 53 publications

(52 citation statements)

References 17 publications

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“…3C-F). Similarly, a reduction in Cx43 has been shown to negatively impact endothelial progenitor cells' ability to migrate, thereby reducing their therapeutic ability [33]. It is apparent from the data presented here that stem cells isolated from Cx43-deficient mice are present in higher numbers and proliferate faster, but are inhibited in their ability to migrate.…”

Section: Cx43 Required For Pluripotency In Skin Stem Cellssupporting

confidence: 50%

Connexin43 Is Required for the Maintenance of Multipotency in Skin-Derived Stem Cells

Dyce

Barr

et al. 2014

Stem Cells and Development

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Expression of the gap junction protein, connexin43 (Cx43), begins early during embryogenesis and is maintained in many different cell types. Several stem cell populations have been shown to express Cx43 and to form functional gap junctions. While it is clear that Cx43 is critical to the function of many organs, whether the same is true for stem cells has not been clearly demonstrated. Recently, stem cells isolated from newborn mouse skin were shown to form oocyte-like cells (OLCs) in vitro, hence the present study focussed on the role Cx43 plays in the proliferation and differentiation of these cells. The stem cells express Cx43 and those from knockout mice (Cx43 KO) exhibited significantly reduced cell-cell coupling. Loss of Cx43 reduced the rate of cellular migration [Cx43 KO, 1.57 -0.65 radial cell units (RCU); wildtype (WT), 5.57 -0.37 RCU] but increased the proliferation rate of the stem cells (Cx43 KO, 29.40% -2.02%; WT, 12.76% -1.50%). The expression of the pluripotency markers OCT4 and Nanog were found to be reduced in the Cx43 KO population, suggesting an inhibition of differentiation potential. To test the differentiation ability, the stem cells were induced to form neuronal cell types in vitro. While both the WT and KO cells were able to form GFAP-positive astrocytic cells, only WT stem cells were able to form bIII tubulin-positive neurons. Similarly, the ability of the stem cells to form OLCs was ablated by the loss of Cx43. These data reveal a role for Cx43 in maintaining multipotency within the skin-derived stem cell population.

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Section: Cx43 Required For Pluripotency In Skin Stem Cellssupporting

confidence: 50%

Connexin43 Is Required for the Maintenance of Multipotency in Skin-Derived Stem Cells

Dyce

Barr

et al. 2014

Stem Cells and Development

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“…It is expressed in endometrium stromal cells during early pregnancy and is necessary for proper uterine angiogenesis and decidualization . The correlation of Cx43 and VEGF expression has been already identified in several studies, considering that reduced expression of Cx43 resulted in decreased expression of VEGF and impaired angiogenic potential …”

Section: Introductionmentioning

confidence: 93%

Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage

Sajjadi

Ghandil

Shahbazian

et al. 2020

J of Obstet and Gynaecol

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Aim Idiopathic recurrent spontaneous miscarriage (IRSM) is one of the pregnancy outcomes that affects 1–2% of women trying to conceive. Specific genotype or aberrant expression of vascular endothelial growth factor A (VEGFA) and connexin 43 (Cx43) as two important genes for embryonic development are deemed to increase the risk of IRSM. Methods To investigate any possible association of VEGFA polymorphisms and aberrant expression of Cx43 and VEGFA with IRSM, we carried out a case–control study including embryo chorionic villus tissues of 100 pregnant women with IRSM and 100 embryo chorionic villus tissues of healthy pregnant women without history of miscarriage. Restriction fragment length polymorphism was used for genotyping of rs699947 (−2578C/A) and rs2010963 (−634G/C) polymorphisms in VEGFA. Besides, quantitative real‐time PCR was performed for VEGFA and Cx43 expression analysis. Results The results showed that the frequency of −634G/C and C/C genotypes was significantly higher in aborted fetuses (P = 0.001 and P < 0.001, respectively) compared to the control group's. However, the frequency of −2578C/A genotypes was not significantly different between the cases and controls. Moreover, a significant higher expression of VEGF (P = 0.0005) and Cx43 (P = 0.0011) was observed in chorionic villus tissues of women with IRSM. Conclusion The finding demonstrated that IRSM frequency may depend on GC and CC genotypes of rs2010963 VEGF polymorphism and expression level of VEGF and Cx43 in IRSM patients was increased.

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“…Additionally, Cx43 knockdown may decrease the expression levels of chemokine (C-C motif) ligand 2 and tumor necrosis factor (TNF)α, and elevate the expression levels of TGF-β1 and collagen α1, which affects the extravasations of neutrophils and macrophages involved in the wound healing process (40). Furthermore, the angiogenic potential of endothelial cells would be impaired following Cx43 knockdown (41,42). Although the role of Cx43 reduction in wound healing has been widely accepted, the underlying mechanism and signaling pathway involved in its function require further investigation to provide a solid theoretical basis for its clinical application.…”

Section: Implications Of Cx43 In Skin Systemmentioning

confidence: 99%

Connexin 43: Key roles in the skin

Zhang

Cui

2017

Biomedical Reports

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Abstract. Gap junctions are tightly packed intercellular channels that serve a common purpose of allowing the intercellular exchange of small metabolites, second messengers and electrical signals. Connexins (Cxs) are gap junction proteins. Currently, 20 and 21 members of Cxs have been characterized in mice and humans, respectively. Connexin 43 (Cx43) is the most ubiquitously expressed type of Cx in the skin. It is produced by various different types of skin cell, such as keratinocytes, fibroblasts, endothelial and basal cells, melanocytes and dermal papilla cells. At present, more evidence indicates that Cx43 has an important role in skin repair and skin tumor development, as well as in skin cell invasion and metastasis. In this review, current knowledge regarding the regulation and function of Cx43 is summarized and the therapeutic potential of regulating Cx43 activity is discussed.

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Reduction of connexin43 in human endothelial progenitor cells impairs the angiogenic potential

Cited by 53 publications

References 17 publications

Connexin43 Is Required for the Maintenance of Multipotency in Skin-Derived Stem Cells

Connexin43 Is Required for the Maintenance of Multipotency in Skin-Derived Stem Cells

Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage

Connexin 43: Key roles in the skin

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