ArticleProceedings of the National Academy of Sciences of the United States of America2020
Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- GHRHR Deficiency Enhances Retinal Ganglion Cell Survival and Visual Functions in Experimental Glaucoma by Inhibiting Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of Growth Hormone (GH) and Other Somatotropic Axis Elements in Retinal Neuroprotection.Current issues in molecular biology · 2026Review
- Therapeutic potential of growth hormone-releasing hormone analogues in cardiovascular and cerebrovascular diseases: mechanisms and preclinical evidence.Frontiers in pharmacology · 2026Review
- Anti-inflammatory action of fluvoxamine in an endotoxin-induced uveitis rat model: Histopathological evidence.Molecular vision · 2026Article
- Growth hormone-releasing hormone in retinal disorders and uveitis: an updated review.International journal of ophthalmology · 2026Review
- Bidirectional Phosphorylation Changes in Opsins Associated With Early Myopia and Hyperopia Signal Regulation by Phosphoproteomics.Investigative ophthalmology & visual science · 2025Article
- Growth hormone - releasing hormone in the immune system.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone receptor (GHRH-R) and its signaling.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone and its analogues in health and disease.Nature reviews. Endocrinology · 2025Review
- Anti-inflammatory potential of Piper betleoides C. DC., a promising Piper species of Northeast India: in vitro and in vivo evidence and mechanistic insight.Inflammopharmacology · 2024Article
- Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis.Frontiers in medicine · 2024Article
- Growth hormone-releasing hormone receptor antagonist MIA-602 attenuates cardiopulmonary injury induced by BSL-2 rVSV-SARS-CoV-2 in hACE2 mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.Nature communications · 2023Article
- Growth hormone-releasing hormone antagonists protect against hydrochloric acid-induced endothelial injury in vitro.Environmental toxicology and pharmacology · 2023Article
- Protective effects of melatonin receptor agonists on endotoxin-induced uveitis in rats.Iranian journal of basic medical sciences · 2023Article
- Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells.Frontiers in immunology · 2023Article
- Growth Hormone-Releasing Hormone in Endothelial Inflammation.Endocrinology · 2022Review
- Growth hormone-releasing hormone receptor signaling in experimental ocular inflammation and neuroprotection.Neural regeneration research · 2022Review
- Ruxolitinib attenuates secondary injury after traumatic spinal cord injury.Neural regeneration research · 2022Article
- Polymorphisms of the Growth Hormone Releasing Hormone Receptor Gene Affect Body Conformation Traits in Chinese Dabieshan Cattle.Animals : an open access journal from MDPI · 2022Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Ocular inflammation is a major cause of visual impairment attributed to dysregulation of the immune system. Previously, we have shown that the receptor for growth-hormone-releasing hormone (GHRH-R) affects multiple inflammatory processes. To clarify the pathological roles of GHRH-R in acute ocular inflammation, we investigated the inflammatory cascades mediated by this receptor. In human ciliary epithelial cells, the NF-κB subunit p65 was phosphorylated in response to stimulation with lipopolysaccharide (LPS), resulting in transcriptional up-regulation of GHRH-R. Bioinformatics analysis and coimmunoprecipitation showed that GHRH-R had a direct interaction with JAK2. JAK2, but not JAK1, JAK3, and TYK2, was elevated in ciliary body and iris after treatment with LPS in a rat model of endotoxin-induced uveitis. This elevation augmented the phosphorylation of STAT3 and production of proinflammatory factors, including IL-6, IL-17A, COX2, and iNOS. In explants of iris and ciliary body, the GHRH-R antagonist, MIA-602, suppressed phosphorylation of STAT3 and attenuated expression of downstream proinflammatory factors after LPS treatment. A similar suppression of STAT3 phosphorylation was observed in human ciliary epithelial cells. In vivo studies showed that blocking of the GHRH-R/JAK2/STAT3 axis with the JAK inhibitor Ruxolitinib alleviated partially the LPS-induced acute ocular inflammation by reducing inflammatory cells and protein leakage in the aqueous humor and by repressing expression of STAT3 target genes in rat ciliary body and iris and in human ciliary epithelial cells. Our findings indicate a functional role of the GHRH-R/JAK2/STAT3-signaling axis in acute anterior uveitis and suggest a therapeutic strategy based on treatment with antagonists targeting this signaling 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.