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Differential Regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 Expression in Airway Epithelium

Center for Comparative Respiratory Biology and Medicine, Department of Pulmonary and Critical Care, and Internal Medicine, University of California at Davis, Davis; and Department of Internal Medicine, University of California at San Francisco, San Francisco, California

Correspondence and requests for reprints should be addressed to Reen Wu, Ph.D., Center for Comparative Respiratory Biology and Medicine, Surge 1, Room 1121, University of California at Davis, One Shields Ave., Davis, CA 95616. E-mail: rwu{at}ucdavis.edu

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 µg/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.

Key Words: airway epithelium • cytokine • JAK/STAT • mucin • Gob-5

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