ArticleStem cell research & therapy2017
Connexin 32 and connexin 43 are involved in lineage restriction of hepatic progenitor cells to hepatocytes.
Article in Stem cell research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- Role of connexin 32 in the directional differentiation of induced pluripotent stem cells into hepatocytes.International journal of medical sciences · 2024Article
- Cellular signaling crosstalk between Wnt signaling and gap junctions inbenzo[a]pyrene toxicity.Cell biology and toxicology · 2023Article
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Connexin 43 Gene Ablation Does Not Alter Human Pluripotent Stem Cell Germ Lineage Specification.Biomolecules · 2021Article
- Connexin Expression Is Altered in Liver Development ofInternational journal of molecular sciences · 2021Article
- MicroRNA-206 relieves irradiation-induced neuroinflammation by regulating connexin 43.Experimental and therapeutic medicine · 2021Article
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBi-potential hepatic progenitor cells can give rise to both hepatocytes and cholangiocytes, which is the last phase and critical juncture in terms of sequentially hepatic lineage restriction from any kind of stem cells. If their differentiation can be controlled, it might access to functional hepatocytes to develop pharmaceutical and biotechnology industries as well as cell therapies for end-stage liver diseases.
methodsIn this study, we investigated the influence of Cx32 and Cx43 on hepatocyte differentiation of WB-F344 cells by in vitro gain and loss of function analyses. An inhibitor of Cx32 was also used to make further clarification. To reveal p38 MAPK pathway is closely related to Cxs, rats with 70% partial hepatectomy were injected intraperitoneally with a p38 inhibitor, SB203580. Besides, the effects of p38 MAPK pathway on differentiation of hepatoblasts isolated from fetal rat livers were evaluated by addition of SB203580 in culture medium.
resultsIn vitro gain and loss of function analyses showed overexpression of Connexin 32 and knockdown of Connexin 43 promoted hepatocytes differentiation from hepatic progenitor cells. In addition, in vitro and ex vivo research revealed inhibition of p38 mitogen-activated protein kinase pathway can improve hepatocytes differentiation correlating with upregulation of Connexin 32 expression and downregulation of Connexin 43 expression.
conclusionsHere we demonstrate that Connexins play crucial roles in facilitating differentiation of hepatic progenitors. Our work further implicates that regulators of Connexins and their related pathways might provide new insights to improve lineage restriction of stem cells to mature hepatocytes.
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