Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury

Low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor for Wnt ligands. Tissue fibrosis is a progressive pathological process with excessive extracellular matrix proteins (ECM) deposition. Myofibroblasts, identified by alpha-smooth muscle actin (aSMA) expression, play an important role in tissue fibrosis by producing ECM production and interacting with immune cells. Here we found that Dickkopf1 (DKK1) induced gene expressions is associated with inflammation and tissue repair in lung fibroblasts. We demonstrated that genetic deletion of LRP6 in aSMA-expressing cells using Acta2-cre Lrp6fl/fl (Lrp6AKO) mice abrogated bleomycin (BLM)-induced lung inflammation and fibrosis phenotype, suggesting a potential role for DKK1-LRP6 axis in modulating fibrotic processes. Our results highlight LRP6's crucial role in fibroblasts in regulating inflammation and fibrosis upon BLM-induced lung injury. Overall design: To investigate DKK-1 mediated gene expression in vitro, in wildtype mouse lung fibroblasts.