MUC1 contributes to goblet cell metaplasia and MUC5AC expression in response to cigarette smoke in vivo.

TitleMUC1 contributes to goblet cell metaplasia and MUC5AC expression in response to cigarette smoke in vivo.
Publication TypeJournal Article
Year of Publication2020
AuthorsKato K, Chang EH, Chen Y, Lu W, Kim MM, Niihori M, Hecker L, Kim KChul
JournalAm J Physiol Lung Cell Mol Physiol
Date Published2020 07 01
KeywordsAnimals, Cell Line, Tumor, Cell Polarity, Epithelial Cells, Epithelium, ErbB Receptors, Goblet Cells, Metaplasia, Mucin 5AC, Mucin-1, Phosphorylation, Rats, Sprague-Dawley, Smoking

Goblet cell metaplasia (GCM) and mucin overproduction are a hallmark of chronic rhinosinusitis (CRS) and chronic obstructive pulmonary disease (COPD). In the airways, cigarette smoke (CS) induces activation of the epidermal growth factor receptor (EGFR) leading to GCM and overexpression of the gel-forming mucin MUC5AC. Although previous studies have demonstrated that a membrane-bound mucin, MUC1, modulates the activation of CS-induced EGFR, the role of MUC1 in CS-induced GCM and mucin overproduction has not been explored. In response to CS exposure, wild-type (WT) rats displayed Muc1 translocation from the apical surface of airway epithelium to the intracellular compartment of hyperplastic intermediate cells, EGFR phosphorylation, GCM, and Muc5ac overproduction. Similarly, human CRS sinonasal tissues demonstrated hyperplasia of intermediate cells enriched with MUC1 in the intracellular compartment, which was accompanied by GCM and increased MUC5AC expression. To further evaluate the role of Muc1 in vivo, a Muc1 knockout (KO) rat (MUC in humans and Muc in animals) was developed. In contrast to WT littermates, Muc1-KO rats exhibited no activation of EGFR, and were protected from GCM and Muc5ac overproduction. Genetic knockdown of MUC1 in human lung or Muc1 knockout in primary rat airway epithelial cells led to significantly diminished EGF-induced MUC5AC production. Together, these findings suggest that MUC1-dependent EGFR activation mediates CS-induced GCM and mucin overproduction. Strategies designed to suppress MUC1-dependent EGFR activation may provide a novel therapeutic approach for treating mucin hypersecretion in CRS and COPD.

Alternate JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID32401676
PubMed Central IDPMC7468848
Grant ListR21 AG061687 / AG / NIA NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
1 I01 BX003919-01A1 / / U.S. Department of Veterans Affairs (VA) / International
I01 BX003919 / BX / BLRD VA / United States
1R21AG061687-01 / GF / NIH HHS / United States
HL-47125 / GF / NIH HHS / United States
Faculty Reference: 
Eugene H. Chang, MD