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 resp...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.展开更多
从含麦迪霉素生物合成基因的初级克隆pCN6C5中,发现并分离了麦迪霉素4″酰化酶基因,与质粒载体p1J680相连,获得重组质粒p66B,在螺旋霉素产生菌中得到表达,其主要产物为4″异戊酰螺旋霉素。以p66B DNA BamHI-BamHI 2.3kb插入片段为探针,...从含麦迪霉素生物合成基因的初级克隆pCN6C5中,发现并分离了麦迪霉素4″酰化酶基因,与质粒载体p1J680相连,获得重组质粒p66B,在螺旋霉素产生菌中得到表达,其主要产物为4″异戊酰螺旋霉素。以p66B DNA BamHI-BamHI 2.3kb插入片段为探针,从麦迪霉素产生菌基因文库中获得了另一阳性克隆pCN10F5,Southern分子杂交确定pCN10F5 BamHI-BamHI 8.0kb为同源片段。以pWHM3及pIJ680为载体,获得重组质粒pWF5及p6F5,分子大小分别为15.2kb及13.3kb。通过DNA转化,并经分子杂交实验证明,获得含重组质粒的螺旋霉素产生菌克隆菌株。其主要产物经分离、纯化后,分析其理化性质和光谱数据,鉴定为丙酰螺旋霉素Ⅲ和Ⅱ。研究还表明,麦迪霉素基因文库中只有pCN10F5 DNA与碳霉素产生菌的4″异戊酰化酶基因同源,提示pCN6C5克隆携带的麦迪霉素4″酰化酶基因与pCN10F5的4″丙酰化酶基因及碳霉素4″异戊酰化酶基因有一定的区别。展开更多
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).
文摘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.
