Interleukin-13 Induces Mucin 5AC Production Involving STAT6/SPDEF in Human Airway Epithelial Cells

Abstract

Mucus hypersecretion is commonly observed in many chronic airway inflammatory diseases. Mucin 5AC (MUC5AC) is a major airway mucin because of its high expression in goblet cells. Here, the authors identified a gene called SAM domain–containing prostate-derived Ets factor (SPDEF) that was induced by interleukin (IL)-13. Their results showed that specific knockdown of SPDEF reduced IL-13-induced MUC5AC expression in human airway epithelial cells. This finding was associated with decreased expression of anterior gradient 2 (AGR2) and Ca²⁺-activated Cl⁻ channel (CLCA1), which regulate IL-13-mediated MUC5AC overproduction. Furthermore, transfection with SPDEF siRNA enhanced expression of forkhead box a2 (Foxa2), a key transcription factor that is known to prevent mucus production. The authors also demonstrated that the repression of STAT6 inhibited expression of SPDEF and MUC5AC induced by IL-13. These results show that SPDEF plays a critical role in regulating a transcriptional network mediating IL-13-induced MUC5AC synthesis dependent on STAT6.

Keywords::

• anterior gradient 2
• Ca²⁺-activated Cl-channel
• forkhead box a2
• interleukin-13
• mucin
• SAM domain–containing prostate-derived Ets factor

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.