title: Inhibition of Notch Signaling Attenuates Schistosomiasis Hepatic Fibrosis via Blocking Macrophage M2 Polarization.
abstract: Macrophages play a key role in the pathogenesis of liver granuloma and fibrosis in schistosomiasis. However, the underlying mechanisms have not been fully characterized. This study revealed that the macrophages infiltrating the liver tissues in a murine model of Schistosoma japonica infection exhibited M2 functional polarization, and Notch1/Jagged1 signaling was significantly upregulated in the M2 polarized macrophages in vivo and in vitro. Furthermore, the blockade of Notch signaling pathway by a γ-secretase inhibitor could reverse macrophage M2 polarization in vitro and alleviate liver granuloma and fibrosis in the murine model of schistosomiasis. These results implied that the Notch1/Jagged1 signaling-dependent M2 polarization of macrophages might play an important role in liver granuloma and fibrosis in schistosomiasis, and the inhibition of Notch1/Jagged1 signaling might provide a novel therapeutic approach to administrate patients with schistosomiasis.
authors.affiliation: Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Peige
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Tumor Pathology, Hainan Cancer Hospital, Affiliated Hospital of Hainan Medical College,Haikou, China.
authors.forename: Shaojiang
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Tumor Pathology, Hainan Cancer Hospital, Affiliated Hospital of Hainan Medical College,Haikou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Weng
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000276:immunology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D000072100:Jagged-1 Protein / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D000067996:RAW 264.7 Cells; D051881:Receptor, Notch1 / Q000276:immunology*; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D053829:Amyloid Precursor Protein Secretases