In support of these findings, E4 decreased FN, COL1α1, and PAI-1 levels in lung tissue cores from patients with pulmonary fibrosis, while increasing MMP-1 and uPA levels (Figure 3E and Supplemental Figure 3, A–C), demonstrating that E4 can reduce established and end-stage lung fibrosis. This evidence concerns the gene PLAU and pulmonary fibrosis.