ArticleJournal of hepatology2017
Human germline hedgehog pathway mutations predispose to fatty liver.
Article in Journal of hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Network toxicology study and key target validation of chlorpyrifos-induced nonalcoholic fatty liver disease.Scientific reports · 2026Article
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- CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.Frontiers in immunology · 2024Review
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- Mechanisms of liver fibrosis in metabolic syndrome.eGastroenterology · 2023Article
- Anti-miR-96 and Hh pathway inhibitor MDB5 synergistically ameliorate alcohol-associated liver injury in mice.Biomaterials · 2023Article
- Protective Effects ofInternational journal of molecular sciences · 2023Article
- [Inhibition of Sonic Hedgehog signaling inhibits fibrous scar formation and adversely affects functional outcome after ischemic brain injury in rats].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- [Transforming growth factor-β1 induces transformation of rat meningeal fibroblasts into myofibroblasts by upregulating Shh signaling].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Case Report: Long-term follow-up of desert hedgehog variant caused 46, XY gonadal dysgenesis with multiple complications in a Chinese child.Frontiers in genetics · 2022Article
- Loss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2.Nature metabolism · 2021Article
- Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis.Gastroenterology · 2020Review
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
- Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Review
- Hedgehog signalling in liver pathophysiology.Journal of hepatology · 2018Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsNon-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway.
methodsPatients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2
resultsPatients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2
conclusionsOur results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous buildup (scar tissue) and inflammation of the liver tissue. For the first time patients with holoprosencephaly, a disease caused by SHH signaling mutations, are shown to have increased liver steatosis independent of obesity. This observation was recapitulated in a mouse model of attenuated SHH signaling that also showed increased liver steatosis but with decreased fibrosis and inflammation. While SHH inhibition is associated with a good NAFLD prognosis, this increase in liver fat accumulation in the context of SHH signaling inhibition must be studied prospectively to evaluate its long-term effects, especially in individuals with Western-type dietary habits.
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