EGF‐Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis of Smoking‐Induced Lesions in the Human Airway Epithelium. (17th November 2016)

• Record Type: Journal Article
• Authors: Zuo, Wu‐Lin; Yang, Jing; Gomi, Kazunori; Chao, IonWa; Crystal, Ronald G.; Shaykhiev, Renat
• Is Part Of: Stem cells. Volume 35:Number 3(2017:Mar.)
• Page Start: 824
• Page End: 837
• Publication Date: 2016-11-17
• Subjects: Airway basal cells -- Epidermal growth factor receptor -- Hyperplasia -- Metaplasia -- Chronic obstructive pulmonary disease; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2512
• Languages: English
• ISSNs: 1066-5099

Abstract

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 Abstract : AREG is upregulated in airway basal stem/progenitor cells (BC) and BC‐derived intermediate cells undergoing smoking‐induced EGF‐mediated squamous differentiation. AREG induces a unique, distinct from EGF, pattern of EGFR activation in BC. AREG promotes BC‐ and mucous cell hyperplasia. AREG suppresses ciliated cell differentiation and decreases barrier integrity. AREG establishes an autocrine self‐amplifying signaling loop in BC.