Xenopus: An alternative model system for identifying muco-active agents.

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PloS one, ISSN: 1932-6203, Vol: 13, Issue: 2, Page: e0193310

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10.1371/journal.pone.0193310; 10.1371/journal.pone.0193310.g005; 10.1371/journal.pone.0193310.g006; 10.1371/journal.pone.0193310.g007; 10.1371/journal.pone.0193310.g002; 10.1371/journal.pone.0193310.g001; 10.1371/journal.pone.0193310.g003; 10.1371/journal.pone.0193310.g004
Hyo Jung Sim; Sang-Hyun Kim; Kyung-Jae Myung; Taejoon Kwon; Hyun-Shik Lee; Tae Joo Park; Wei-Chun Chin
Public Library of Science (PLoS); Figshare; PUBLIC LIBRARY SCIENCE
Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Biochemistry; Medicine; Cell Biology; Genetics; Physiology; Pharmacology; Biotechnology; Immunology; Developmental Biology; Cancer; Science Policy; 59999 Environmental Sciences not elsewhere classified; 69999 Biological Sciences not elsewhere classified; 39999 Chemical Sciences not elsewhere classified; Several muco-active agents; alternative model system; Xenopus laevis embryos; vivo model system; vivo model systems; novel screening technique; airway goblet cells; lung epithelial cell line; mucus secretion; DNA; muco-active agents; Current muco-active reagents control mucus secretion; COPD; muco-active reagents
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The airway epithelium in human plays a central role as the first line of defense against environmental contaminants. Most respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, and respiratory infections, disturb normal muco-ciliary functions by stimulating the hypersecretion of mucus. Several muco-active agents have been used to treat hypersecretion symptoms in patients. Current muco-active reagents control mucus secretion by modulating either airway inflammation, cholinergic parasympathetic nerve activities or by reducing the viscosity by cleaving crosslinking in mucin and digesting DNAs in mucus. However, none of the current medication regulates mucus secretion by directly targeting airway goblet cells. The major hurdle for screening potential muco-active agents that directly affect the goblet cells, is the unavailability of in vivo model systems suitable for high-throughput screening. In this study, we developed a high-throughput in vivo model system for identifying muco-active reagents using Xenopus laevis embryos. We tested mucus secretion under various conditions and developed a screening strategy to identify potential muco-regulators. Using this novel screening technique, we identified narasin as a potential muco-regulator. Narasin treatment of developing Xenopus embryos significantly reduced mucus secretion. Furthermore, the human lung epithelial cell line, Calu-3, responded similarly to narasin treatment, validating our technique for discovering muco-active reagents.