Title | |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Zuo W-L, Yang J, Gomi K, Chao IW, Crystal RG, Shaykhiev R |
Journal | Stem Cells |
Volume | 35 |
Issue | 3 |
Pagination | 824-837 |
Date Published | 2017 Mar |
ISSN | 1549-4918 |
Abstract | The airway epithelium of cigarette smokers undergoes dramatic remodeling with hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia, altered ciliated cell differentiation and decreased junctional barrier integrity, relevant to chronic obstructive pulmonary disease and lung cancer. In this study, we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) is induced by smoking in human airway epithelium as a result of epidermal growth factor (EGF)-driven squamous differentiation of airway BC stem/progenitor cells. In turn, AREG induced a unique EGFR activation pattern in human airway BC, distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered ciliated cell differentiation and impaired barrier integrity. Further, AREG promoted its own expression and suppressed expression of EGF, establishing an autonomous self-amplifying signaling loop in airway BC relevant for promotion of EGF-independent hyperplastic phenotypes. Thus, EGF-AREG interplay in airway BC stem/progenitor cells is one of the mechanisms that mediates the interconnected pathogenesis of all major smoking-induced lesions in the human airway epithelium. Stem Cells 2017;35:824-837. |
DOI | 10.1002/stem.2512 |
Alternate Journal | Stem Cells |
PubMed ID | 27709733 |
PubMed Central ID | PMC5330845 |
Grant List | UL1 RR024143 / RR / NCRR NIH HHS / United States R01 HL127393 / HL / NHLBI NIH HHS / United States R01 HL123544 / HL / NHLBI NIH HHS / United States R01 HL107882 / HL / NHLBI NIH HHS / United States UL1 TR000457 / TR / NCATS NIH HHS / United States |