ArticleLiver international : official journal of the International Association for the Study of the Liver2013
Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 64 citations in OpenAlex.
- Hedgehog blockade in steroid-refractory sclerotic chronic graft-versus-host disease.British journal of haematology · 2021Trial
- Parasites as Modulators of Angiogenesis: Implications for Vascular Biology and Pathogenesis.Pathogens (Basel, Switzerland) · 2026Review
- Anti-aging effect of Hedgehog signaling.Experimental & molecular medicine · 2026Review
- Implications of host sex on liver metabolism duringFrontiers in cellular and infection microbiology · 2026Review
- Mechanism and Progress of Natural Products in the Treatment of NAFLD-Related Fibrosis.Molecules (Basel, Switzerland) · 2023Review
- M2 macrophages mediate fibrotic scar formation in the early stages after cerebral ischemia in rats.Neural regeneration research · 2023Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.Cellular and molecular gastroenterology and hepatology · 2023Article
- The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time.International journal of molecular sciences · 2021Review
- Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis.Advanced drug delivery reviews · 2021Review
- Liver sinusoidal endothelial cells are implicated in multiple fibrotic mechanisms.Molecular biology reports · 2021Review
- Role of metaplasia during gastric regeneration.American journal of physiology. Cell physiology · 2020Review
- Macrophage transcriptome modification induced by hypoxia and lactate.Experimental and therapeutic medicine · 2019Article
- Macrophages in Systemic Sclerosis: Novel Insights and Therapeutic Implications.Current rheumatology reports · 2019Review
- Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Review
- The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018Review
- Hedgehog signalling in liver pathophysiology.Journal of hepatology · 2018Review
- Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses.Frontiers in immunology · 2018Review
- Host Regulators of Liver Fibrosis During Human Schistosomiasis.Frontiers in immunology · 2018Review
- Frontline Science: Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma.Journal of leukocyte biology · 2017Article
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15 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundSchistosomiasis mansoni is a major cause of portal fibrosis and portal hypertension. The Hedgehog pathway regulates fibrogenic repair in some types of liver injury.
aimsDetermine if Hedgehog pathway activation occurs during fibrosis progression in schistosomiasis and to determine if macrophage-related mechanisms are involved.
methodsImmunohistochemistry 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.
resultsPatients 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.
conclusionSEA stimulates liver macrophages to produce Hh ligands, which promote alternative activation of macrophages, fibrogenesis and vascular remodelling in schistosomiasis.
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