Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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PDZ Peptide of the ZO-1 Protein Significantly Increases UTP-Induced MUC8 Anti-Inflammatory Mucin Overproduction in Human Airway Epithelial Cells

  • Han Seo (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Hyun-Chae Lee (Department of Medical Science, Kosin University College of Medicine) ;
  • Ki Chul Lee (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Doosik Kim (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Jiwook Kim (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Donghee Kang (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Hyung-Joo Chung (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Hee-Jae Cha (Department of Genetics, Kosin University College of Medicine) ;
  • Jeongtae Kim (Department of Anatomy, Kosin University College of Medicine) ;
  • Kyoung Seob Song (Department of Medical Science, Kosin University College of Medicine)
  • Received : 2023.07.03
  • Accepted : 2023.09.03
  • Published : 2023.11.30
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Abstract

Mucus hyperproduction and hypersecretion are observed often in respiratory diseases. MUC8 is a glycoprotein synthesized by epithelial cells and generally expressed in the respiratory track. However, the physiological mechanism by which extracellular nucleotides induce MUC8 gene expression in human airway epithelial cells is unclear. Here, we show that UTP could induce MUC8 gene expression through P2Y2-PLCβ3-Ca2+ activation. Because the full-length cDNA sequence of MUC8 has not been identified, a specific siRNA-MUC8 was designed based on the partial cDNA sequence of MUC8. siRNA-MUC8 significantly increased TNF-α production and decreased IL-1Ra production, suggesting that MUC8 may downregulate UTP/P2Y2-induced airway inflammation. Interestingly, the PDZ peptide of ZO-1 protein strongly abolished UTP-induced TNF-α production and increased IL-1Ra production and MUC8 gene expression. In addition, the PDZ peptide dramatically increased the levels of UTP-induced ZO proteins and TEER (trans-epithelial electrical resistance). These results show that the anti-inflammatory mucin MUC8 may contribute to homeostasis, and the PDZ peptide can be a novel therapeutic candidate for UTP-induced airway inflammation.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2021R1A4A1031380 to H.J.C. [Hee-Jae Cha], J.K. [Jeongtae Kim], and K.S.S.).

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