American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2020
Comparative StudyGWAS Functional Variant rs2076295 Regulates Desmoplakin (DSP) Expression in Airway Epithelial Cells.
Rationale: Genetic association studies have identified rs2076295 in association with idiopathic pulmonary fibrosis (IPF). We hypothesized that rs2076295 is the functional variant regulating DSP (desmoplakin) expression in human bronchial epithelial cells, and DSP regulates extracellular matrix-related gene expression and cell migration, which is relevant to IPF development. Objectives: To determine whether rs2076295 regulates DSP expression and the function of DSP in airway epithelial cells. ⋯ Silencing of MMP7 and MMP9 abolished increased migration in DSP-knockout cells. Conclusions: rs2076295 regulates DSP expression in human airway epithelial cells. The loss of DSP enhances extracellular matrix-related gene expression and promotes cell migration, which may contribute to the pathogenesis of IPF.