ArticleHepatology (Baltimore, Md.)2016
Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 82 citations in OpenAlex.
- Discovery of pyrrolo[2,3-d]pyrimidine derivatives with inhibitory effect on liver cancer stem cell.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Sonic Hedgehog-Gli1 signaling promotes microglial activation via the IKKβ/NF-κB pathway.Acta pharmacologica Sinica · 2026Article
- Impact of Hedgehog modulators on signaling pathways in primary murine and human hepatocytes in vitro: insights into liver metabolism.Archives of toxicology · 2025Article
- Cryo-electron microscopy for GPCR research and drug discovery in endocrinology and metabolism.Nature reviews. Endocrinology · 2024Review
- Reappraisal of the Roles of the Sonic Hedgehog Signaling Pathway in Hepatocellular Carcinoma.Cancers · 2024Review
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- Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma.International journal of molecular sciences · 2023Article
- Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis.Clinical and molecular hepatology · 2023Review
- Effects of oleoylethanolamide supplementation on inflammatory biomarkers, oxidative stress and antioxidant parameters of obese patients with NAFLD on a calorie-restricted diet: A randomized controlled trial.Frontiers in pharmacology · 2023Article
- Sonidegib Suppresses Production of Inflammatory Mediators and Cell Migration in BV2 Microglial Cells and Mice Treated with Lipopolysaccharide via JNK and NF-κB Inhibition.International journal of molecular sciences · 2022Article
- Inhibition of Hedgehog Delays Liver Regeneration through Disrupting the Cell Cycle.Current issues in molecular biology · 2022Article
- Mesenchymal Stem Cells Influence Activation of Hepatic Stellate Cells, and Constitute a Promising Therapy for Liver Fibrosis.Biomedicines · 2021Review
- Loss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2.Nature metabolism · 2021Article
- Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.Advanced drug delivery reviews · 2021Review
- Hedgehog dysregulation contributes to tissue-specific inflammaging of resident macrophages.Aging · 2021Article
- Procyanidin B2 alleviates liver injury caused by cold stimulation through Sonic hedgehog signalling and autophagy.Journal of cellular and molecular medicine · 2021Article
- The hedgehog pathway suppresses neuropathogenesis in CD4 T cell-driven inflammation.Brain : a journal of neurology · 2021Article
- Maladaptive regeneration - the reawakening of developmental pathways in NASH and fibrosis.Nature reviews. Gastroenterology & hepatology · 2021Review
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
unlabelledHedgehog (Hh) signaling plays a critical role in liver development, regeneration, injury repair, and carcinogenesis. Activation of Hh signaling has been observed in patients with nonalcoholic fatty liver diseases (NAFLD); however, the pathobiological function and regulatory mechanism of hepatic Hh signaling in the pathogenesis of NAFLD remain to be further defined. This study was designed to examine the effect and mechanism of hepatic Hh signaling in high-fat diet-induced NAFLD by using pharmacological Smoothened (Smo) inhibitors (GDC-0449 and LED225) and liver-specific Smo knockout mice. Administration of Smo inhibitors to high-fat diet-fed wild-type mice significantly reduced the numbers of activated macrophages and decreased the expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein 1, and interleukin-6) as assessed by F4/80 immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, respectively. The Smo inhibitors were noted to have variable effects on hepatic fat accumulation. Liver-specific deletion of Smo also reduced macrophage activation and inhibited proinflammatory cytokine expression, while it did not significantly alter fat accumulation in the liver. Mechanistically, we found that activation of glioma-associated oncogene 1 by Hh signaling in primary hepatocytes increased the production of osteopontin, which subsequently enhanced the macrophage-mediated proinflammatory response through paracrine signaling.
conclusionHepatocyte Hh signaling can promote liver inflammation through osteopontin-mediated macrophage activation; this mechanism importantly contributes to the progression of NAFLD.
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