Prevention of fatal hepatic complication in schistosomiasis by inhibition of CETP  

作　　者：Shinji Yokoyama Kuniko Okumura-Noji Rui Lu 

机构地区：[1]Nutritional Health Science Research Center,Chubu University

出　　处：《The Journal of Biomedical Research》2015年第3期176-188,共13页生物医学研究杂志（英文版）

基　　金：supported in part by MEXT-Supported Program for the Strategic Research Foundation at Private Universities(S1201007);Grant-in-aid from MEXT Japan(24614018)

摘　　要：Schistosoma japonicum, once endemic all the East Asia, remains as a serious public health problem in certain regions. Ectopic egg embryonation in the liver causes granulomatosis and eventually fatal cirrhosis, so that prevention of this process is one of the keys to reduce its mortality. The embryonation requires cholesteryl ester from HDL of the host blood for egg yolk formation, and this reaction is impaired from the abnormal large HDL in genetic cholesteryl ester transfer protein （CETP） deficiency. When CETP was expressed in mice that otherwise lack this protein, granulomatosis of the liver was shown increased compared to the wild type upon infec- tion of Schistosoma japonicum. The CETP deficiencies accumulated exclusively in East Asia, from Indochina to Siberia, so that Shistosomiasis can be a screening factor for this accumulation. CD36 related protein （CD36RP） was identified as a protein for this reaction, cloned from the cDNA library of Schistosoma japonicum with 1880-bp encoding 506 amino acids. The antibody against the extracellular loop of CD36RP inhibited cholesteryl ester uptake from HDL and suppressed egg embryonation in culture. Therefore, inhibition of CETP is a potential approach to prevent liver granulomatosis and thereby fatal liver cirrhosis in the infection of Schistosoma japonicum.Schistosoma japonicum, once endemic all the East Asia, remains as a serious public health problem in certain regions. Ectopic egg embryonation in the liver causes granulomatosis and eventually fatal cirrhosis, so that prevention of this process is one of the keys to reduce its mortality. The embryonation requires cholesteryl ester from HDL of the host blood for egg yolk formation, and this reaction is impaired from the abnormal large HDL in genetic cholesteryl ester transfer protein （CETP） deficiency. When CETP was expressed in mice that otherwise lack this protein, granulomatosis of the liver was shown increased compared to the wild type upon infec- tion of Schistosoma japonicum. The CETP deficiencies accumulated exclusively in East Asia, from Indochina to Siberia, so that Shistosomiasis can be a screening factor for this accumulation. CD36 related protein （CD36RP） was identified as a protein for this reaction, cloned from the cDNA library of Schistosoma japonicum with 1880-bp encoding 506 amino acids. The antibody against the extracellular loop of CD36RP inhibited cholesteryl ester uptake from HDL and suppressed egg embryonation in culture. Therefore, inhibition of CETP is a potential approach to prevent liver granulomatosis and thereby fatal liver cirrhosis in the infection of Schistosoma japonicum.

关 键 词：Schistosoma japonicum liver cirrhosis GRANULOMATOSIS CETP deficiency HDL cholesteryl ester 

分 类 号：R532.21[医药卫生—内科学]