| Author | Pereira, Thiago de Almeida | |
| Author | Xie, Guanhua | |
| Author | Choi, Steve S. | |
| Author | Syn, Wing-Kin | |
| Author | Voieta, Izabela | |
| Author | Lu, Jiuyi | |
| Author | Chan, Isaac S. | |
| Author | Swiderska, Marzena | |
| Author | Amaral, Kirsten B. | |
| Author | Antunes, Carlos Mauricio de Figueiredo | |
| Author | Secor, William E. | |
| Author | Witek, Rafal P. | |
| Author | Lambertucci, José Roberto | |
| Author | Pereira, Fausto Edmundo Lima | |
| Author | Diehl, Anna Mae | |
| Access date | 2016-07-26T12:13:18Z | |
| Available date | 2016-07-26T12:13:18Z | |
| Document date | 2012 | |
| Citation | PEREIRA, T. A. et al. Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni. Liver International, v. 33, n. 1, p. 149-161, 2012. | pt_BR |
| ISSN | 1478-3223 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/15121 | |
| Language | eng | pt_BR |
| Publisher | Wiley | pt_BR |
| Rights | open access | pt_BR |
| Title | Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1111/liv.12016 | |
| Abstract | Schistosomiasis mansoni is a major cause of portal fibrosis and portal hypertension. The Hedgehog pathway regulates fibrogenic repair in some types of liver injury. Aims: Determine if Hedgehog pathway activation
occurs during fibrosis progression in schistosomiasis and to determine if
macrophage-related mechanisms are involved. Methods: Immunohistochemistry
was used to characterize the cells that generate and respond to
Hedgehog ligands in 28 liver biopsies from patients with different grades of
schistosomiasis fibrosis staged by ultrasound. Cultured macrophages
(RAW264.7 and primary rat Kupffer cells) and primary rat liver sinusoidal
endothelial cells (LSEC) were treated with schistosome egg antigen (SEA)
and evaluated using qRT-PCR. Inhibition of the Hedgehog pathway was used
to investigate its role in alternative activation of macrophages (M2) and vascular
tube formation. Results: Patients with schistosomiasis expressed more
ligands (Shh and Ihh) and target genes (Patched and Gli2) than healthy individuals.
Activated LSEC and myofibroblasts were Hedgehog responsive [Gli2
(+)] and accumulated in parallel with fibrosis stage (P < 0.05). Double IHC
for Ihh/CD68 showed that Ihh(+) cells were macrophages. In vitro studies
demonstrated that SEA-stimulated macrophages to express Ihh and Shh
mRNA (P < 0.05). Conditioned media from such macrophages induced
luciferase production by Shh-LightII cells (P < 0.001) and Hedgehog inhibitors
blocked this effect (P < 0.001). SEA-treated macrophages also up-regulated
their own expression of M2 markers, and Hh pathway inhibitors
abrogated this response (P < 0.01). Inhibition of the Hedgehog pathway in
LSEC blocked SEA-induced migration and tube formation. Conclusion: SEA
stimulates liver macrophages to produce Hh ligands, which promote alternative
activation of macrophages, fibrogenesis and vascular remodelling in
schistosomiasis. | pt_BR |
| Affilliation | Duke University Medical Center Durham. Department of Medicine. Division of Gastroenterology. NC, USA / Fundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Duke University Medical Center Durham. Department of Medicine. Division of Gastroenterology. NC, USA | pt_BR |
| Affilliation | Duke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, NC, USA / Durham Veteran Affairs Medical Center Durham. Department of Medicine. Section of Gastroenterology. NC, USA | pt_BR |
| Affilliation | Duke University Medical Center Durham. Department of Medicine. Division of Gastroenterology. NC, USA / Institute of Hepatology London. Foundation for Liver Research. UK, London | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Duke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, NC, USA | pt_BR |
| Affilliation | Duke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, NC, USA | pt_BR |
| Affilliation | Duke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, NC, USA | pt_BR |
| Affilliation | Centers for Disease Control and Prevention Atlanta. GA, USA | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Centers for Disease Control and Prevention Atlanta. GA, USA | pt_BR |
| Affilliation | Life Technologies Durham. NC, USA | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo Vitória. Núcleo de Doenças Infecciosas. Centro de Ciências da Saúde. Vitória, ES, Brasil | pt_BR |
| Affilliation | Duke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, NC, USA | pt_BR |
| Subject | Allternative activation of macrophages | pt_BR |
| Subject | Fibrosis | pt_BR |
| Subject | Hedgehog pathway | pt_BR |
| Subject | Schistosomiasis mansoni | pt_BR |
| Subject | Vascular remodelling | pt_BR |
