Figure 2.

Schematic of CLCA1-driven MCM in human airways based on the current literature. IL-13 induces CLCA1 gene expression through activated STAT6. CLCA1 protein is expressed, is secreted, and undergoes proteolytic self-cleavage to yield two fragments (N-CLCA1: N-terminal fragment; C-CLCA1: C-terminal fragment). N-CLCA1 engages and activates the CaCC TMEM16A. Downstream, a signaling pathway is activated through MAPK13 which leads to induction of the inflammatory mucin MUC5AC, followed by goblet cell differentiation and subsequent MCM. It is currently unknown whether or how the steps highlighted in the dashed ellipse (CLCA1 cleavage and activation of TMEM16A) contribute to the activation of MAPK13.