ArticleThe Journal of biological chemistry2013
Activation of the transcription factor GLI1 by WNT signaling underlies the role of SULFATASE 2 as a regulator of tissue regeneration.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Heparan sulfate chains in hepatocellular carcinoma.Gastroenterology report · 2025Review
- MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer.BMC cancer · 2023Article
- The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis.Frontiers in endocrinology · 2023Review
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- Sulfatase 2 Along with Syndecan 1 and Glypican 3 Serum Levels are Associated with a Prognostic Value in Patients with Alcoholic Cirrhosis-Related Advanced Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2022Article
- Wnt/-Catenin Signaling and Liver Regeneration: Circuit, Biology, and Opportunities.Gene expression · 2021Review
- Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- The extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex.The Journal of biological chemistry · 2020Article
- Luminescent and fluorescent triple reporter plasmid constructs for Wnt, Hedgehog and Notch pathway.PloS one · 2019Article
- Liver regeneration requires Yap1-TGFβ-dependent epithelial-mesenchymal transition in hepatocytes.Journal of hepatology · 2018Article
- Epithelial Deletion of Sulf2 Exacerbates Bleomycin-Induced Lung Injury, Inflammation, and Mortality.American journal of respiratory cell and molecular biology · 2017Article
- The "in and out" of glucosamine 6-O-sulfation: the 6th sense of heparan sulfate.Glycoconjugate journal · 2017Review
- Transcriptional Induction of Periostin by a Sulfatase 2-TGFβ1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma.Cancer research · 2017Article
- Hedgehog and TGFβ signaling converge on Gli2 to control bony invasion and bone destruction in oral squamous cell carcinoma.Oncotarget · 2016Article
- Review
- WNT5A inhibits hepatocyte proliferation and concludes β-catenin signaling in liver regeneration.The American journal of pathology · 2015Article
- Cooperative integration between HEDGEHOG-GLI signalling and other oncogenic pathways: implications for cancer therapy.Expert reviews in molecular medicine · 2015Review
- SULF2, a heparan sulfate endosulfatase, is present in the blood of healthy individuals and increases in cirrhosis.Clinica chimica acta; international journal of clinical chemistry · 2015Article
- The transcription factor GLI1 modulates the inflammatory response during pancreatic tissue remodeling.The Journal of biological chemistry · 2014Article
- Tri-iodothyronine induces hepatocyte proliferation by protein kinase A-dependent β-catenin activation in rodents.Hepatology (Baltimore, Md.) · 2014Article
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Tissue regeneration requires the activation of a set of specific growth signaling pathways. The identity of these cascades and their biological roles are known; however, the molecular mechanisms regulating the interplay between these pathways remain poorly understood. Here, we define a new role for SULFATASE 2 (SULF2) in regulating tissue regeneration and define the WNT-GLI1 axis as a novel downstream effector for this sulfatase in a liver model of tissue regeneration. SULF2 is a heparan sulfate 6-O-endosulfatase, which releases growth factors from extracellular storage sites turning active multiple signaling pathways. We demonstrate that SULF2-KO mice display delayed regeneration after partial hepatectomy (PH). Mechanistic analysis of the SULF2-KO phenotype showed a decrease in WNT signaling pathway activity in vivo. In isolated hepatocytes, SULF2 deficiency blocked WNT-induced β-CATENIN nuclear translocation, TCF activation, and proliferation. Furthermore, we identified the transcription factor GLI1 as a novel target of the SULF2-WNT cascade. WNT induces GLI1 expression in a SULF2- and β-CATENIN-dependent manner. GLI1-KO mice phenocopied the SULF2-KO, showing delayed regeneration and decreased hepatocyte proliferation. Moreover, we identified CYCLIN D1, a key mediator of cell growth during tissue regeneration, as a GLI1 transcriptional target. GLI1 binds to the cyclin d1 promoter and regulates its activity and expression. Finally, restoring GLI1 expression in the liver of SULF2-KO mice after PH rescues CYCLIN D1 expression and hepatocyte proliferation to wild-type levels. Thus, together these findings define a novel pathway in which SULF2 regulates tissue regeneration in part via the activation of a novel WNT-GLI1-CYCLIN D1 pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.