Gene regulatory roles for lysyl oxidases in the context of BPD

We report, for the first time a transcriptome-wide analysis of gene regulation by lysyl oxidases. In the context of primary mouse lung fibroblasts, siRNA knockdown of Lox, Loxl1, and Loxl2 deregulated the expression of 134, 3,761 and 3,554 genes, respectively. Identified lysyl oxidases target-genes relevant to lung development and BPD included Mmp3, Mmp9, Eln, Rarres1, Gdf10, Ifnb1, Cxcl2, and Cxcl9. The expression of target-genes in vivo correlated with the lysyl oxidases expression in a mouse model of BPD. Moreover, using BAPN, we demonstrated that the transcriptional regulation by lysyl oxidases was independent of catalytic activity both in vitro and in vivo, which is of importance in targeting the lysyl oxidases in a therapeutic context.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung and Airway Developmental Biology Source Type: research