ArticleJournal of autoimmunity2018
Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis.
Article in Journal of autoimmunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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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, 30 citations in OpenAlex.
- Androgen dysregulates the follicular extracellular matrix and increases pro-fibrotic gene expression in the mouse ovary.Scientific reports · 2026Article
- Review
- Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy.International journal of molecular sciences · 2024Review
- Article
- Axl regulated survival/proliferation network and its therapeutic intervention in mouse models of glomerulonephritis.Arthritis research & therapy · 2022Article
- Elevated expression of TAM receptor tyrosine kinase in synovial fluid and synovial tissue of rheumatoid arthritis.Clinical and experimental immunology · 2022Article
- Drugging the efferocytosis process: concepts and opportunities.Nature reviews. Drug discovery · 2022Review
- Article
- The Akt-mTORC1 pathway mediates Axl receptor tyrosine kinase-induced mesangial cell proliferation.Journal of leukocyte biology · 2022Article
- Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma.CNS neuroscience & therapeutics · 2020Article
- Article
- Autoimmunity in 2018.Clinical reviews in allergy & immunology · 2019Article
- AXL targeting reduces fibrosis development in experimental unilateral ureteral obstruction.Physiological reports · 2019Article
- Repression of AXL expression by AP-1/JNK blockage overcomes resistance to PI3Ka therapy.JCI insight · 2019Article
- PD-1 immunobiology in systemic lupus erythematosus.Journal of autoimmunity · 2019Review
- Review
- Gas6/TAM Receptors in Systemic Lupus Erythematosus.Disease markers · 2019Review
- Serum Axl predicts histology-based response to induction therapy and long-term renal outcome in lupus nephritis.PloS one · 2019Article
- Mesangioproliferative Kidney Diseases and Platelet-Derived Growth Factor-Mediated AXL Phosphorylation.Kidney medicineArticle
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Glomerulonephritis (GN) is a typical lesion in autoantibody and immune complex disorders, including SLE. Because the Gas6/Axl pathway has been implicated in the pathogenesis of many types of GN, targeting this pathway might ameliorate GN. Consequently, we have studied the efficacy and mechanism of R428, a potent selective Axl inhibitor, in the prevention of experimental anti-GBM nephritis. Axl upregulation was investigated with Sp1/3 siRNA in the SV40-transformed mesangial cells. For Axl inhibition, a daily dose of R428 (125 mg/kg) or vehicle was administered orally. GN was induced with anti-GBM sera. Renal disease development was followed by serial blood urine nitrogen (BUN) determinations and by evaluation of kidney histology at the time of sacrifice. Axl-associated signaling proteins were analyzed by Western blotting and inflammatory cytokine secretion was analyzed by Proteome array. SiRNA data revealed the transcription factor Sp1 to be an important regulator of mesangial Axl expression. Anti-GBM serum induced severe nephritis with azotemia, protein casts and necrotic cell death. R428 treatment diminished renal Axl expression and improved kidney function, with significantly decreased BUN and glomerular proliferation. R428 treatment inhibited Axl and significantly decreased Akt phosphorylation and renal inflammatory cytokine and chemokine expression; similar effects were observed in anti-GBM antiserum-treated Axl-KO mice. These studies support a role for Axl inhibition in glomerulonephritis.
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Registered trials
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