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. 2019 Dec 26;117(2):1139–1147. doi: 10.1073/pnas.1912109117

Fig. 5.

Fig. 5.

Circadian factors are associated with IPF, where a REVERB ligand represses collagen secretion. (A) Odds ratio (OR) for the association between pulmonary fibrosis and sleep duration (OR ± 95% confidence interval (CI); logistic regression; n = 500,074 subjects from the UK Biobank). (B) Changes in clock-gene expression in IPF compared to control subjects from a previously published genome array (GSE47460) (fold change ± 95% confidence interval; n = 90 controls and 98 patients with IPF). (C) qPCR for αSMA (ACTA2) and Collagen1 (COL1A1) following TGFβ stimulation (2 ng/mL) in primary human lung fibroblasts obtained from patients with pulmonary fibrosis in the presence or absence of GSK4112 (10 μM) (n = 4 fibrotic patients). *P < 0.05 (Student t test; mean ± SEM). (D) qPCR for αSMA (ACTA2) expression following treatment with TGFβ (2 ng/mL) and GSK4112 (10 μM) in human PCLS (n = 5 patients). *P < 0.05 (Student t test; mean ± SEM). (E) Enzyme-linked immunosorbent assay analysis of secreted collagen-1 in TGFβ-stimulated PCLS obtained from 3 patients with IPF treated with the REVERB ligand GSK4112 (10 μM) and an Alk5 inhibitor (1 μM) as positive control (n = 3). *P < 0.05 (paired Student t test; mean ± SEM).