Background:Pulmonary fibrosis is an irreversible lung disorder that currently has a limited number of effective therapeutic strategies.Taraxasterol(TAR),a bioactive triterpenoid isolated from plants used in traditiona...Background:Pulmonary fibrosis is an irreversible lung disorder that currently has a limited number of effective therapeutic strategies.Taraxasterol(TAR),a bioactive triterpenoid isolated from plants used in traditional Chinese medicine(TCM),possesses anti-inflammatory and antioxidant activities.However,its precise role in pulmonary fibrosis remains incompletely defined.This study aimed to elucidate whether TAR alleviates pulmonary fibrosis by modulating Protein Phosphatase 2 Scaffold Subunit Abeta(PPP2R1B)expression.Methods:A bleomycininduced murine model of pulmonary fibrosis and a transforming growth factor-β1(TGF-β1)stimulated mouse lung fibroblast cell line(MLg)were established.To evaluate the effects of TARon PPP2R1B expression and markers associated with fibrosis,histopathological staining,quantitative real-time PCR,Western blotting,and immunofluorescence were utilized.Additionally,si-PPP2R1B was used to validate its role in TAR-mediated anti-fibrotic effects.Results:5μg/mL TAR significantly suppressed 5 ng/mL TGF-β1-induced fibroblast activation,migration,and collagen deposition by downregulating PPP2R1B expression(p<0.05).In vivo experiments demonstrated that 10 mg/kg TAR treatment improved alveolar structural integrity,reduced collagen accumulation,and suppressed the secretion of inflammatory cytokines(including TGF-β1,CTGF,TNF-α,and IL-1β)(p<0.05).The concurrent improvement in these key histological and biochemical markers of pulmonary fibrosis indicates that TAR holds strong therapeutic potential for enhancing lung function.Furthermore,si-PPP2R1B confirmed the pivotal role of PPP2R1B in TAR anti-fibrotic action(p<0.05).Conclusion:TAR ameliorates pulmonary fibrosis by downregulating PPP2R1B expression,which consequently attenuates TGF-β1-stimulated fibroblast activation,migration,and collagen deposition in vitro,and reduces collagen accumulation and inflammatory cytokine release in bleomycin-induced murine model of pulmonary fibrosis in vivo.展开更多
文摘Background:Pulmonary fibrosis is an irreversible lung disorder that currently has a limited number of effective therapeutic strategies.Taraxasterol(TAR),a bioactive triterpenoid isolated from plants used in traditional Chinese medicine(TCM),possesses anti-inflammatory and antioxidant activities.However,its precise role in pulmonary fibrosis remains incompletely defined.This study aimed to elucidate whether TAR alleviates pulmonary fibrosis by modulating Protein Phosphatase 2 Scaffold Subunit Abeta(PPP2R1B)expression.Methods:A bleomycininduced murine model of pulmonary fibrosis and a transforming growth factor-β1(TGF-β1)stimulated mouse lung fibroblast cell line(MLg)were established.To evaluate the effects of TARon PPP2R1B expression and markers associated with fibrosis,histopathological staining,quantitative real-time PCR,Western blotting,and immunofluorescence were utilized.Additionally,si-PPP2R1B was used to validate its role in TAR-mediated anti-fibrotic effects.Results:5μg/mL TAR significantly suppressed 5 ng/mL TGF-β1-induced fibroblast activation,migration,and collagen deposition by downregulating PPP2R1B expression(p<0.05).In vivo experiments demonstrated that 10 mg/kg TAR treatment improved alveolar structural integrity,reduced collagen accumulation,and suppressed the secretion of inflammatory cytokines(including TGF-β1,CTGF,TNF-α,and IL-1β)(p<0.05).The concurrent improvement in these key histological and biochemical markers of pulmonary fibrosis indicates that TAR holds strong therapeutic potential for enhancing lung function.Furthermore,si-PPP2R1B confirmed the pivotal role of PPP2R1B in TAR anti-fibrotic action(p<0.05).Conclusion:TAR ameliorates pulmonary fibrosis by downregulating PPP2R1B expression,which consequently attenuates TGF-β1-stimulated fibroblast activation,migration,and collagen deposition in vitro,and reduces collagen accumulation and inflammatory cytokine release in bleomycin-induced murine model of pulmonary fibrosis in vivo.
