ArticleMolecular endocrinology (Baltimore, Md.)2009
Negative regulation of Hedgehog signaling by liver X receptors.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Identification of Differentially Expressed Proteins in the Serum of Colorectal Cancer Patients Using 2D-DIGE Proteomics Analysis.Pathology oncology research : POR · 2016Trial
- Autism spectrum disorder and the role of nuclear hormone receptors: insights and therapeutic implications.Frontiers in neuroscience · 2025Review
- Sterols, Oxysterols, and Accessible Cholesterol: Signalling for Homeostasis, in Immunity and During Development.Frontiers in physiology · 2021Review
- The wHole Story About Fenestrations in LSEC.Frontiers in physiology · 2021Review
- Induction of Stearoyl-CoA 9-Desaturase 1 Protects Human Mesenchymal Stromal Cells Against Palmitic Acid-Induced Lipotoxicity and Inflammation.Frontiers in endocrinology · 2019Article
- Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway.Journal of lipid research · 2018Article
- Isolation and Differentiation of Mesenchymal Stem Cells From Broiler Chicken Compact Bones.Frontiers in physiology · 2018Article
- Evaluating the oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol in periodontal regeneration using periodontal ligament stem cells and alveolar bone healing models.Stem cell research & therapy · 2017Article
- Inhibition of Pancreatic Cancer Cell-Induced Paracrine Hedgehog Signaling by Liver X Receptor Agonists and Oxy16, a Naturally Occurring Oxysterol.Journal of cellular biochemistry · 2017Article
- Liver X receptor α is essential for the capillarization of liver sinusoidal endothelial cells in liver injury.Scientific reports · 2016Article
- Identification of a Chrysanthemic Ester as an Apolipoprotein E Inducer in Astrocytes.PloS one · 2016Article
- Activation of liver X receptors inhibits hedgehog signaling, clonogenic growth, and self-renewal in multiple myeloma.Molecular cancer therapeutics · 2014Article
- Hormonal modulators of glial ABCA1 and apoE levels.Journal of lipid research · 2013Article
- Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling.The Journal of biological chemistry · 2012Article
- Structure-activity relationships for side chain oxysterol agonists of the hedgehog signaling pathway.ACS medicinal chemistry letters · 2012Article
- The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors.Endocrinology · 2011Article
- Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR.Molecular and cellular endocrinology · 2011Article
- Sterol regulation of metabolism, homeostasis, and development.Annual review of biochemistry · 2011Review
- Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2010Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Hedgehog (Hh) signaling is indispensable in embryonic development, and its dysregulated activity results in severe developmental disorders as shown by genetic models of naturally occurring mutations in animal and human pathologies. Hh signaling also functions in postembryonic development and adult tissue homeostasis, and its aberrant activity causes various human cancers. Better understanding of molecular regulators of Hh signaling is of fundamental importance in finding new strategies for pathway modulation. Here, we identify liver X receptors (LXRs), members of the nuclear hormone receptor family, as previously unrecognized negative regulators of Hh signaling. Activation of LXR by specific pharmacological ligands, TO901317 and GW3965, inhibited the responses of pluripotent bone marrow stromal cells and calvaria organ cultures to sonic Hh, resulting in the inhibition of expression of Hh-target genes, Gli1 and Patched1, and Gli-dependent transcriptional activity. Moreover, LXR ligands inhibited sonic Hh-induced differentiation of bone marrow stromal cells into osteoblasts. Elimination of LXRs by small interfering RNA inhibited ligand-induced inhibition of Hh target gene expression. Furthermore, LXR ligand did not inhibit Hh responsiveness in mouse embryonic fibroblasts that do not express LXRs, whereas introduction of LXR into these cells reestablished the inhibitory effects. Daily oral administration of TO901317 to mice after 3 d significantly inhibited baseline Hh target-gene expression in liver, lung, and spleen. Given the importance of modulating Hh signaling in various physiological and pathological settings, our findings suggest that pharmacological targeting of LXRs may be a novel strategy for Hh pathway modulation.
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Registered trials
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.