ArticleLife sciences2018
Slit2-Robo2 signaling modulates the fibrogenic activity and migration of hepatic stellate cells.
Article in Life sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Circadian Dysregulation in Aging Alters Senescence and Inflammatory Pathways in a Sex- and Time-of-Day-Dependent Manner.bioRxiv : the preprint server for biology · 2026Article
- Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Genetic risk variants implicate impaired maintenance and repair of periodontal tissues as causal for periodontitis-A synthesis of recent findings.Periodontology 2000 · 2025Review
- Prognostic model of fibroblasts in idiopathic pulmonary fibrosis by combined bulk and single-cell RNA-sequencing.Heliyon · 2024Article
- Downregulation of Roundabout guidance receptor 2 suppresses hepatocellular carcinoma progression by interacting with Y-box binding protein 1.Scientific reports · 2024Article
- Cell-autonomous action ofFrontiers in molecular neuroscience · 2024Article
- Significance of CCNs in liver regeneration.Journal of cell communication and signaling · 2023Review
- The SLIT/ROBO Pathway in Liver Fibrosis and Cancer.Biomolecules · 2023Review
- CCN2/CTGF promotes liver fibrosis through crosstalk with the Slit2/Robo signaling.Journal of cell communication and signaling · 2023Article
- Role of the SLIT-ROBO signaling pathway in renal pathophysiology and various renal diseases.Frontiers in physiology · 2023Review
- Article
- Soluble TREM-1, as a new ligand for the membrane receptor Robo2, promotes hepatic stellate cells activation and liver fibrosis.Journal of cellular and molecular medicine · 2021Article
- Transcriptional regulation of alcohol induced liver fibrosis in a translational porcine hepatocellular carcinoma model.Biochimie · 2021Article
- Crosstalk between the activated Slit2-Robo1 pathway and TGF-β1 signalling promotes cardiac fibrosis.ESC heart failure · 2021Article
- Identification of Liver Immune Microenvironment-Related Hub Genes in Liver of Biliary Atresia.Frontiers in pediatrics · 2021Article
- SLIT2/ROBO1-signaling inhibits macropinocytosis by opposing cortical cytoskeletal remodeling.Nature communications · 2020Article
- Peripheral blood proteomic profiling of idiopathic pulmonary fibrosis biomarkers in the multicentre IPF-PRO Registry.Respiratory research · 2019Observational
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimSlit/Robo signaling was originally identified as a repulsive guidance cue in regulating axon branching and neuronal migration. Hepatic stellate cells (HSCs) are the key fibrogenic cells in the liver, which are migratory when activated, and express neural crest markers. The aim of the present study was to investigate the functional significance of Slit/Robo signaling in liver fibrogenesis and in HSCs. KEY
findingsBy transcriptomic analysis it was found that axon guidance signaling pathways were significantly upregulated in both diethylnitrosamine (DEN) and thioacetamide (TAA)-induced experimental liver fibrosis. The up-regulation of the ligand Slit2 and membrane receptor Robo2 genes within this pathway was further validated in TAA-induced fibrotic livers. By immunofluorescence staining, Robo2 was localized in fibrotic septa of fibrotic liver and on the surface of HSCs. By Western blot analysis, recombinant Slit2 (rSlit2) was found to promote fibrogenic protein expression in JS1 cells, an immortalized mouse HSC line, while activating PI3K/Akt signaling pathway. This effect was abrogated by LY294002, a PI3K/Akt pathway inhibitor. In addition, rSlit2 stimulation markedly inhibited JS1 cells migration in transwell migration assays, which was abrogated by small interfering RNA (siRNA) knockdown of Robo2 in the cells. SIGNIFICANCE: The present study provides evidence that Slit2/Robo2 signaling mediates the pathogenesis of hepatic fibrogenesis and regulates HSCs biology, thus providing potential markers for HSCs, and therapeutic and diagnostic target toward liver fibrosis.
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