Cystic echinococcosis (CE) treatment urgently requires a novel drug. The p38 mitogen-activated protein kinases (MAPKs) are a family of Ser/Thr protein kinases, but still have to be characterized in Echinococcus granulosus. We identified a 1,107 bp cDNA encoding a 368 amino acid MAPK protein (Egp38) in E. granulosus. Egp38 exhibits 2 distinguishing features of p38-like kinases: a highly conserved T-X-Y motif and an activation loop segment. Structural homology modeling indicated a conserved structure among Egp38, EmMPK2, and H. sapiens p38α, implying a common binding mechanism for the ligand domain and downstream signal transduction processing similar to that described for p38α. Egp38 and its phosphorylated form are expressed in the E. granulosus larval stages vesicle and protoscolices during intermediate host infection of an intermediate host. Treatment of in vitro cultivated protoscolices with the p38-MAPK inhibitor ML3403 effectively suppressed Egp38 activity and led to significant protoscolices death within 5 days. Treatment of in vitro-cultivated protoscolices with TGF-β1 effectively induced Egp38 phosphorylation. In summary, the MAPK, Egp38, was identified in E. granulosus, as an anti-CE drug target and participates in the interplay between the host and E. granulosus via human TGF-β1.
In vitro Scolicidal Efficacy of 5-Fluorouracil and Radiation Against Protoscoleces of Echinococcus granulosus Sensu Lato Pengfei Lu, Jun Li, Rui Mao, Hongzhi Qi, Liping Yang, Qin Zhou, Mengxiao Tian, Wenbao Zhang, Yongxing Bao Acta Parasitologica.2022; 67(2): 820. CrossRef
Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine Yingfang Yu, Jun Li, Weisi Wang, Tian Wang, Wenjing Qi, Xueting Zheng, Lei Duan, Jiaxu Chen, Shizhu Li, Xiumin Han, Wenbao Zhang, Liping Duan BMC Genomics.2021;[Epub] CrossRef
Knock Down the Egp38 and Combine with Radiation to Increase Its Inhibitory Effect on Echinococcus granulosus Pengfei Lu, Mengxiao Tian, Na Yi, Rui Mao, Hongzhi Qi, Liping Yang, Qin Zhou, Jun Li, Wenbao Zhang, Yongxing Bao SSRN Electronic Journal .2021;[Epub] CrossRef
Identification of Functional MKK3/6 and MEK1/2 Homologs from Echinococcus granulosus and Investigation of Protoscolecidal Activity of Mitogen-Activated Protein Kinase Signaling Pathway Inhibitors
In Vitro
and
Chuanshan Zhang, Jing Li, Tuerganaili Aji, Liang Li, Xiaojuan Bi, Ning Yang, Zhide Li, Hui Wang, Rui Mao, Guodong Lü, Yingmei Shao, Dominique A. Vuitton, Hao Wen, Renyong Lin Antimicrobial Agents and Chemotherapy.2019;[Epub] CrossRef
Echinococcosis: Advances in the 21st Century Hao Wen, Lucine Vuitton, Tuerhongjiang Tuxun, Jun Li, Dominique A. Vuitton, Wenbao Zhang, Donald P. McManus Clinical Microbiology Reviews.2019;[Epub] CrossRef
To investigate the potential role of transforming growth factor (TGF)-β1 in liver fibrosis during Echinococcus granulosus infection, 96 BALB/c mice were randomly divided into 2 groups, experimental group infected by intraperitoneal injection with a metacestode suspension and control group given sterile physiological saline. The liver and blood samples were collected at days 2, 8, 30, 90, 180, and 270 post infection (PI), and the expression of TGF-β1 mRNA and protein was determined by real-time quantitative RT-PCR and ELISA, respectively. We also evaluated the pathological changes in the liver during the infection using hematoxylin and eosin (H-E) and Masson staining of the liver sections. Pathological analysis of H-E stained infected liver sections revealed liver cell edema, bile duct proliferation, and structural damages of the liver as evidenced by not clearly visible lobular architecture of the infected liver, degeneration of liver cell vacuoles, and infiltration of lymphocytes at late stages of infection. The liver tissue sections from control mice remained normal. Masson staining showed worsening of liver fibrosis at the end stages of the infection. The levels of TGF-β1 did not show significant changes at the early stages of infection, but there were significant increases in the levels of TGF-β1 at the middle and late stages of infection (P<0.05). RT-PCR results showed that, when compared with the control group, TGF-β1 mRNA was low and comparable with that in control mice at the early stages of infection, and that it was significantly increased at day 30 PI and remained at high levels until day 270 PI (P<0.05). The results of this study suggested that increased expression of TGF-β1 during E. granulosus infection may play a significant role in liver fibrosis associated with E. granulosus infection.
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