Home Blog of Signal Transduction GPCR & G Protein S1P Receptor Effect of FTY-720 on Pulmonary Fibrosis in Mice via the TGF-β1 Signaling Pathway and Autophagy

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Effect of FTY-720 on Pulmonary Fibrosis in Mice via the TGF-β1 Signaling Pathway and Autophagy

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY- 720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

 

Comments：

Based on the results of the study, it appears that FTY-720 has a significant effect on bleomycin-induced pulmonary fibrosis. The drug was found to inhibit the TGF-β1 pathway and up-regulate autophagy, resulting in attenuation of disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice.

Moreover, FTY-720 treatment reduced the levels of IL-1β, TNF-α, and IL-6 cytokines in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were also significantly reduced. In addition, the drug effectively inhibited the expressions of key proteins in the TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins.

These results suggest that FTY-720 is a potential target for treating pulmonary fibrosis and may provide a new mechanism for suppressing this disease. The study was conducted using both in vivo and in vitro assays, providing further evidence of the drug's efficacy in treating pulmonary fibrosis.

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Cat.No. Product Name Information
S5002 Fingolimod (FTY720) HCl Fingolimod (FTY720, Fingolimod Hydrochloride) HCl is a S1P antagonist with IC50 of 0.033 nM in K562, and NK cells. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation.

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S1P Receptor