Mandatory Role of HMGA1 in Human Airway Epithelial Normal Differentiation and Post-injury Regeneration

Background: High mobility group AT-hook1 (HMGA1) is essential for airway basal cell mucociliary differentiation, barrier integrity and wound repair. HMGA1 expression suppresses the abnormal basal cell differentiation to squamous, inflammatory and epithelial-mesenchymal transition phenotype commonly observed in association with cigarette smoking and chronic obstructive pulmonary disease (COPD).Results: HMGA1 knockdown experiments indicate that when HMGA1 expression is suppressed, the airway basal cells cannot normally differentiate into a mucociliary epithelium, form an intact barrier, and repair following injury. Instead, airway basal cell differentiation was skewed to an abnormal squamous EMT-like phenotype associated with airway remodeling in COPD.This study demonstrates that HMGA1 plays a key role in normal airway differentiation, regeneration of the normal airway epithelium following injury, and suppression of expression of genes related to squamous metaplasia, EMT and inflammation.