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Exposure to mold proteases stimulates mucin production in airway epithelial cells through Ras/Raf1/ERK signal pathway.

ABSTRACT: Environmental mold (fungus) exposure poses a significant threat to public health by causing illnesses ranging from invasive fungal diseases in immune compromised individuals to allergic hypertensive diseases such as asthma and asthma exacerbation in otherwise healthy people. However, the molecular pathogenesis has not been completely understood, and treatment options are limited. Due to its thermo-tolerance to the normal human body temperature, Aspergillus. fumigatus (A.fumigatus) is one of the most important human pathogens to cause different lung fungal diseases including fungal asthma. Airway obstruction and hyperresponsiveness caused by mucus overproduction are the hallmarks of many A.fumigatus induced lung diseases. To understand the underlying molecular mechanism, we have utilized a well-established A.fumigatus extracts (AFE) model to elucidate downstream signal pathways that mediate A.fumigatus induced mucin production in airway epithelial cells. AFE was found to stimulate time- and dose-dependent increase of major airway mucin gene expression (MUC5AC and MUC5B) partly via the elevation of their promoter activities. We also demonstrated that EGFR was required but not sufficient for AFE-induced mucin expression, filling the paradoxical gap from a previous study using the same model. Furthermore, we showed that fungal proteases in AFE were responsible for mucin induction by activating a Ras/Raf1/ERK signaling pathway. Ca2+ signaling, but ROS, both of which were stimulated by fungal proteases, was an indispensable determinant for ERK activation and mucin induction. The discovery of this novel pathway likely contributes to our understanding of the pathogenesis of fungal sensitization in allergic diseases such as fungal asthma.

SUBMITTER: Wu X

PROVIDER: S-EPMC7176129 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exposure to mold proteases stimulates mucin production in airway epithelial cells through Ras/Raf1/ERK signal pathway.

Wu Xianxian X Lee Boram B Zhu Lingxiang L Ding Zhi Z Chen Yin Y

PloS one 20200422 4

Environmental mold (fungus) exposure poses a significant threat to public health by causing illnesses ranging from invasive fungal diseases in immune compromised individuals to allergic hypertensive diseases such as asthma and asthma exacerbation in otherwise healthy people. However, the molecular pathogenesis has not been completely understood, and treatment options are limited. Due to its thermo-tolerance to the normal human body temperature, Aspergillus. fumigatus (A.fumigatus) is one of the ...[more]

PMID: 32320453

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Dataset Information

Exposure to mold proteases stimulates mucin production in airway epithelial cells through Ras/Raf1/ERK signal pathway.

Publications

Exposure to mold proteases stimulates mucin production in airway epithelial cells through Ras/Raf1/ERK signal pathway.

Similar Datasets

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