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Cellular signaling crosstalk between Wnt signaling and gap junctions inbenzo[a]pyrene toxicity.
Won, Dong-Hoon; Hwang, Da-Bin; Shin, Yoo-Sub; Kim, Shin-Young; Kim, Changuk; Hong, In-Sun; Kang, Byeong-Cheol; Che, Jeong-Hwan; Yun, Jun-Won.
Afiliación
  • Won DH; Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea.
  • Hwang DB; Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea.
  • Shin YS; Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea.
  • Kim SY; Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea.
  • Kim C; Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea.
  • Hong IS; Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 21999, South Korea.
  • Kang BC; Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, 03080, South Korea.
  • Che JH; Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, 03080, South Korea. casache@snu.ac.kr.
  • Yun JW; Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea. jwyun@catholic.ac.kr.
Cell Biol Toxicol ; 39(1): 165-182, 2023 02.
Article en En | MEDLINE | ID: mdl-34283317
Gap junctional intercellular communication (GJIC) is considered a key biological mechanism to maintain homeostasis in cell differentiation and growth. In addition, as another major signaling pathway associated with cell proliferation and differentiation, Wnt/ß-catenin signaling appears to trigger several cellular responses against injury. The purpose of the present study was to investigate the effects of a known toxic agent, benzo[a]pyrene (BaP), on the regulation and interaction between GJIC and Wnt/ß-catenin signaling. BaP treatment resulted in GJIC inhibition and decreases the major GJIC protein connexin 43 (Cx43) in WB-F344 rat liver epithelial cells. We also found BaP-mediated downregulation of Wnt/ß-catenin signaling related to the PI3K-Akt pathway. To identify the relationship between GJIC and Wnt/ß-catenin signaling, we treated WB-F344 cells with the Wnt agonist CHIR99021 and found that it inhibited GJIC while causing a significant reduction in Cx43 expression at both the mRNA and protein levels, through the repression of promoter activity. This Wnt agonist-mediated GJIC inhibition was confirmed using a small interfering RNA directed against the Wnt antagonist Dact2, indicating that Wnt/ß-catenin signaling negatively regulates GJIC. Despite the inverse correlation between Wnt/ß-catenin signaling and Cx43 promoter activation as indicated by downregulation of ß-catenin nuclear translocation and upregulation of Cx43 promoter activation involving HNF3ß, BaP treatment decreased the Cx43 protein expression, which was associated with protein degradation, possibly through protein kinase C activation. In conclusion, our results revealed the mechanism of BaP-induced inhibition of GJIC and Wnt/ß-catenin signaling. More importantly, linking Wnt/ß-catenin signaling to Cx protein expression will have profound implications in understanding the relationships among different major signaling pathways associated with cell proliferation and differentiation in toxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conexina 43 / Beta Catenina Límite: Animals Idioma: En Revista: Cell Biol Toxicol Asunto de la revista: TOXICOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conexina 43 / Beta Catenina Límite: Animals Idioma: En Revista: Cell Biol Toxicol Asunto de la revista: TOXICOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Suiza