Mechanism of Lung Fibrosis Caused by Rare Earth Samarium Oxide Through Hippo Signaling Pathway and the Intervention of GBE.

With the ongoing advancement and utilization of rare earth elements, human and environmental exposure to these materials has risen substantially. Samarium oxide (Sm₂O₃), a rare earth element, has been shown to induce pulmonary fibrosis, but the mechanisms are not clear. This study aimed to investigate the primary mechanisms by which rare earth SmO contributes to pulmonary fibrosis in relation to the Hippo signaling pathway and to assess the interventional effects of Ginkgo biloba extract (GBE). A mouse model of pulmonary fibrosis was established through intratracheal administration of a SmO suspension, while human embryonic lung fibroblasts were also treated for intervention studies. The results indicated that compared with the control group, the expression of SAV1, LATS1/2, MST1, YAP1, and TEAD1 genes was significantly up-regulated in the SmO group, while the expression of TAZ gene was down-regulated. Additionally, the levels of p-LATS1, LATS1, YAP, and p-YAP were elevated, suggesting that SmO promotes pulmonary fibrosis through an imbalance and abnormal regulation of the Hippo signaling pathway. Furthermore, human embryonic lung fibroblasts stained with SmO were treated with different dose gradients of GBE, and the expression level of p-LATS1, LATS1, YAP, and p-YAP was decreased as the dose of SmO increased, whereas treatment with GBE increased the expression of these proteins. GBE can mitigate the fibrotic response induced by Sm₂O₃ exposure. These findings demonstrate that Sm₂O₃ induces pulmonary fibrosis, at least in part, by inactivating the Hippo signaling pathway. Further investigation is warranted to fully elucidate the protective mechanisms of GBE and its therapeutic potential in this context.