ArticleNature communications2024
Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
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- Targeted Delivery of Nucleic Acid Therapeutics: Emerging Carriers and Applications in Common Metabolic and Inflammatory Diseases.International journal of nanomedicine · 2026Review
- [Current research progress status in identifying hepatocellular ballooning degeneration in nonalcoholic steatohepatitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Immunopathogenic mechanisms and immunoregulatory therapies in MASLD.Cellular & molecular immunology · 2025Review
- Chronic Nanoplastic Exposure Promotes the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Palmitic acid reduces LDLR-dependent uptake of macrophage-derived extracellular vesicles by hepatoma cells.Non-coding RNA research · 2025Article
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- Immunomodulatory Tissue Factors in the Gallbladder Walls of Pediatric Patients with Chronic Calculous Cholecystitis.Children (Basel, Switzerland) · 2025Article
- Integrative Analysis of Key Signalling Pathways in Neural Tube Defects: From Molecular Mechanisms to Therapeutic Strategies.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2025Review
- Inhibition of Differentiation of 3T3-L1 Cells by Increasing Glioma-Associated Oncogene Expression inPreventive nutrition and food science · 2024Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sonic hedgehog (SHH) and heat shock protein 90β (HSP90β) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90β is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90β ubiquitylation through deubiquitylase USP31, thus preventing HSP90β degradation and promoting hepatic lipid synthesis. HSP90β significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90β axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90β-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.
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