A non-redundant role for Serpinb3a in the induction of mucus production in asthma (141.17)

Asthma is a major public health burden worldwide. Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production remain largely unknown and therapies to effectively target mucus hypersecretion are lacking. Using a murine asthma model, we showed that SerpinB3a, the mouse ortholog of the serine protease inhibitors, SERPINB4 and B3, contribute to house dust mite induced airway hyperresponsiveness (AHR), mucus production and goblet cell hyperplasia and expression of SPDEF, a transcription factor that mediates goblet cell differentiation. Microarray analysis revealed attenuated expression of multiple IL-13 regulated genes that contribute to mucus production in the Serpinb3a null mice and IL-13 treated mice showed attenuated AHR and mucus production. Our data have revealed a novel non-redundant role for SERPINB4 and B3 in mediating mucus production through regulation of SPDEF expression.