Differential regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 expression in airway epithelium.
This study demonstrates that the two biomarkers, MUC5AC/ Muc5ac and hCLCA1/Gob5, which are frequently associated with surface mucous/goblet cells in asthmatic airways, are differentially regulated. Intratracheal instillation of IL-13 (0.5 mug/mouse lung) elicited 8- and 110-fold induction of Muc5ac and Gob5 messages, respectively, within 24 h in wild-type mouse lung, whereas these inductions were abrogated in Stat6 knockout mice. The induction of MUC5AC/Muc5ac message could not be duplicated in vitro with primary tracheobronchial epithelial (TBE) cells derived from wild-type mice or humans, despite significant inductions still seen for hCLCA1/Gob5. Further studies with JAK inhibitors and STAT6 signaling showed active signaling of the JAK/STAT6 pathway in these primary TBE cultures by IL-13 in the regulation of hCLCA1 expression. Dual immunofluorescent staining with antibodies specific to MUC5AC and hCLCA1 revealed a differential nature of the expression of these two biomarkers by distinct cell types of primary TBE cultures. Finally, MUC5AC expression could be elevated by a bacterial product, peptidoglycan, without any induction of hCLCA1. Thus, these results suggest that the two biomakers of the metaplastic airway mucous cell type are differentially regulated by JAK/STAT6-dependent and -independent pathways.
Thai
Philip
P
Center for Comparative Respiratory Biology and Medicine, Surge 1, Room 1121, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
Chen
Yin
Y
Dolganov
Gregory
G
Wu
Reen
R
D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D053613:Janus Kinase 1; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D009088:Mucoproteins / Q000235:genetics* / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000502:physiology; D014132:Trachea / Q000166:cytology / Q000276:immunology / Q000378:metabolism
C492109:CLCA1 protein, human; D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D004791:Enzyme Inhibitors; D018793:Interleukin-13; C524678:MUC5AC protein, human; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D009088:Mucoproteins; D010457:Peptidoglycan; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1