ArticleThe Journal of clinical investigation2001
TNF-alpha downregulates murine hepatic growth hormone receptor expression by inhibiting Sp1 and Sp3 binding.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 105 citations in OpenAlex.
- Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.The Journal of clinical endocrinology and metabolism · 2018Trial
- The effects of tissue inflammation on cancer cachexia.Biochimica et biophysica acta. Molecular basis of disease · 2026Review
- A Theoretical Link Between the GH/IGF-1 Axis and Cytokine Family in Children: Current Knowledge and Future Perspectives.Children (Basel, Switzerland) · 2025Review
- A novel link between chronic inflammation and humanin regulation in children.Frontiers in endocrinology · 2023Article
- IGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome.Cell reports · 2022Article
- Pathogenesis of Musculoskeletal Deficits in Children and Adults with Inflammatory Bowel Disease.Nutrients · 2021Review
- The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury.International journal of molecular sciences · 2021Article
- An adverse outcome pathway for immune-mediated and allergic hepatitis: a case study with the NSAID diclofenac.Archives of toxicology · 2020Article
- Tumor Necrosis Factor Alpha Regulates Skeletal Myogenesis by Inhibiting SP1 Interaction withMolecular and cellular biology · 2020Article
- Chronic inflammation and the growth hormone/insulin-like growth factor-1 axis.Central-European journal of immunology · 2020Review
- Signal Transduction for TNFα-Induced Type II SOCS Expression and Its Functional Implication in Growth Hormone Resistance in Carp Hepatocytes.Frontiers in endocrinology · 2020Article
- Growth Hormone Receptor Gene Expression Increase Reflects Nutritional Status Improvement in Patients Affected by Crohn's Disease.Frontiers in pediatrics · 2018Article
- Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis.International journal of molecular sciences · 2017Article
- Growth Hormone Resistance-Special Focus on Inflammatory Bowel Disease.International journal of molecular sciences · 2017Review
- Mice with infectious colitis exhibit linear growth failure and subsequent catch-up growth related to systemic inflammation and IGF-1.Nutrition research (New York, N.Y.) · 2017Article
- Gene environment interaction in periphery and brain converge to modulate behavioral outcomes: Insights from the SP1 transient early in life interference rat model.World journal of psychiatry · 2016Review
- Immunogenomics reveal molecular circuits of diclofenac induced liver injury in mice.Oncotarget · 2016Article
- TNF-α-induced NF-κB activation upregulates microRNA-150-3p and inhibits osteogenesis of mesenchymal stem cells by targeting β-catenin.Open biology · 2016Article
- Distinct mechanisms of induction of hepatic growth hormone resistance by endogenous IL-6, TNF-α, and IL-1β.American journal of physiology. Endocrinology and metabolism · 2014Article
- Sarcopenia and cachexia: the adaptations of negative regulators of skeletal muscle mass.Journal of cachexia, sarcopenia and muscle · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Children with chronic inflammatory diseases experience growth failure and wasting. This may be due to growth hormone resistance caused by cytokine-induced suppression of growth hormone receptor (GHR) gene expression. However, the factors governing inflammatory regulation of GHR are not known. We have reported that Sp1 and Sp3 regulate hepatic GHR expression. We hypothesized that TNF-alpha suppresses GHR expression by inhibiting Sp1/Sp3 transactivators. LPS administration significantly reduced murine hepatic GHR expression, as well as Sp1 and Sp3 binding to GHR promoter cis elements. TNF-alpha was integral to this response, as LPS did not affect hepatic Sp1/Sp3 binding or GHR expression in TNF receptor 1-deficient mice. TNF-alpha treatment of BNL CL.2 mouse liver cells reduced Sp1 and Sp3 binding to a GHR promoter cis element and downregulated activity of a GHR promoter-driven luciferase reporter. Combined mutations within adjacent Sp elements eliminated GHR promoter suppression by TNF-alpha without affecting overall nuclear levels of Sp1 or Sp3 proteins. These studies demonstrate that murine GHR transcription is downregulated by LPS, primarily via TNF-alpha-dependent signaling. Evidence suggests that inhibition of Sp transactivator binding is involved. Further investigation of these mechanisms may identify novel strategies for preventing inflammatory suppression of growth.
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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.