Airway goblet cell differentiation and related mucus overproduction are critical processes in the development of respiratory diseases, including asthma. The underlying mechanisms, however, are not fully understood. We identified Runt-related transcription factor 2 (Runx2) as a novel regulator for goblet cell differentiation. Runx2 was up-regulated by 6.4-fold during IL-13-induced goblet cell differentiation of human bronchial epithelial cells. Knockdown of Runx2 attenuated the IL-13-induced differentiation/mucus production by 67%. Mechanistically, Runx2 bound to the promoter of SAM-pointed domain-containing Ets-like factor (SPDEF), a known factor for goblet cell differentiation, resulting in an activation of SPDEF transcription. In vivo, Runx2 was induced by 6.2-fold in pulmonary epithelium of house dust mite-challenged mice. Blockade of Runx2 inhibited the house dust mite-induced goblet cell differentiation with a 75% reduction in mucus overproduction while improving airway responsiveness to methacholine by 41%. More importantly, a 12.3-fold increase in Runx2 expression was observed in human asthma lung epithelium, underlying the potential clinical importance of these findings.-Shi, N., Zhang, J., Chen, S.-Y. Runx2, a novel regulator for goblet cell differentiation and asthma development.
Keywords: SPDEF; airway epithelial remodeling; mucus overproduction; transcriptional activation.
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