Runx2, a novel regulator for goblet cell differentiation and asthma development

Abstract

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.