摘要
Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin I(ISP I)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis.According to our results,ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP I.ISP I through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carrimycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides potential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.
基金
supported by the Beijing Natural Science Foundation,China(Grant No.:7222118)
the National Natural Science Foundation of China(Grant No.:82073900)
the CAMS Innovation Fund for Medical Sciences,China(CIFMS,Grant Nos.:2021-I2M-1-030,and 2021-I2M-1-028).
