The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice

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Sci. Signal.  18 Apr 2017:
Vol. 10, Issue 475, eaai8583
DOI: 10.1126/scisignal.aai8583

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Drugging a transcription factor to treat asthma

In the lungs of asthma patients, too many goblet cells differentiate (a process called metaplasia) and consequently produce excess mucus in response to various inflammatory signals. The transcription factor FOXM1 is upstream of the transcription factor SPDEF, which is important for airway goblet cell differentiation. Sun et al. identified and characterized a small molecule called RCM-1 that prevented the nuclear translocation of FOXM1 in mice sensitized to house dust mite allergens. In these mice, RCM-1 also prevented airway hyperreactivity and inflammation and improved lung function. IL-13 signaling triggers goblet cell metaplasia, and RCM-1 prevented this response in mice that received IL-13 intranasally. Thus, RCM-1 could be used to treat asthma and other chronic pulmonary disorders associated with goblet cell metaplasia.