title: 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 Ca(2+)-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.
authors.affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D055271:Mucin 5AC / Q000096:biosynthesis*; D009088:Mucoproteins; D015513:Oncogene Proteins; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D034741:RNA, Small Interfering; D020545:Respiratory Mucosa / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000235:genetics*
chemical_list: C502296:AGR2 protein, human; C492109:CLCA1 protein, human; D018118:Chloride Channels; C496502:FOXA2 protein, human; D018793:Interleukin-13; D055271:Mucin 5AC; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D050783:Proto-Oncogene Proteins c-ets; D034741:RNA, Small Interfering; C403974:SPDEF protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D051542:Hepatocyte Nuclear Factor 3-beta