Calycosin attenuates pulmonary fibrosis by the epithelial-mesenchymal transition repression upon inhibiting the AKT/GSK3β/β-catenin signaling pathway

xlomafota13 shared this article with you from Inoreader Calycosin attenuates pulmonary fibrosis by the epithelial-mesenchymal transition repression upon inhibiting the AKT/GSK3β/β-catenin signaling pathway Via histochem Acta Histochem. 2021 Jun 30;123(5):151746. doi: 10.1016/j.acthis.2021.151746. Online ahead of print. ABSTRACT The precise etiology and pathogenesis of idiopathic pulmonary fibrosis are not completely understood, and no satisfactory treatment exists. This work aimed to examine the effects of calycosin (CA, an isoflavone compound) on pulmonary fibrosis (PF) and explore the underlying mechanism. In this study, we established a mice model of PF induced by 5 mg/mL bleomycin (BLM) , and mice were orally administrated with 7 mg/kg or 14 mg/kg CA once a day for three weeks. In vitro, after pretreated with 80 μM CA, MLE-12 cells were stimulated with 10 ng/mL transforming growth factor-β1 (TGF-β1) for inducing epithelial-mesenchymal transition (EMT). The results showed that CA treatment ameliorated the severity of fibrosis and the lung tissue damage, as well as suppressed the secretion of inflammation factors in a dose-dependent manner of the PF mice model induced by BLM. Subsequently, CA inhibited the BLM-induced PF progression by repressing EMT, evidenced by the reverse of the downregulation of E-cadherin and the upregulation of vimentin, α-SMA, and fibronectin. Moreover, the elevated phosphorylation of AKT and GSK3β induced by BLM (or TGF-β1) was decreased by CA treatment, leading to the rescue of the high expression of β-catenin. CA prevented the translocation of β-catenin from the cytoplasm to the nucleus. The repressed effects of CA on the TGF-β1-i nduced EMT and the AKT/GSK3β/β-catenin axis, as well as the translocation of β-catenin were all reversed by a AKT activator SC79. Taken together, CA ameliorated PF by the EMT inhibition upon suppressing the AKT/GSK3β/β-catenin signaling pathway. PMID:34217047 | DOI:10.1016/j.acthis.2021.151746 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.