Role of the JAK/STAT pathway in a streptozotocin-induced diabetic retinopathy mouse model
| Autor: | Chan-Ho Cho, Kug-Hwan Roh, Na-Young Lim, Sung Jae Park, SaeGwang Park, Hyun Woong Kim |
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| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
Diabetic Retinopathy Sensory Systems Streptozocin Mice Inbred C57BL Cellular and Molecular Neuroscience Ophthalmology Mice STAT Transcription Factors Disease Models Animal Glucose STAT5 Transcription Factor Diabetes Mellitus Animals Tyrosine Janus Kinase Inhibitors RNA Messenger Phosphorylation Janus Kinases Signal Transduction |
| Zdroj: | Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 260(11) |
| ISSN: | 1435-702X |
| Popis: | The Janus tyrosine kinase and signal transducers and activators of transcription (JAK/STAT) pathway is involved in vascular endothelial growth factor (VEGF) expression, but the role of this pathway in diabetic retinopathy (DR) remains unclear. We investigated the role of the JAK/STAT pathway on DR and VEGF expression using a streptozotocin (STZ)-induced DR mouse model.Cultured ARPE-19 cells were exposed to high-glucose conditions and treated with JAK/STAT inhibitors (JAK inhibitor I [JAKiI], tofacitinib, STAT3 inhibitor [STAT3i]) for 48 h. Reverse-transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to investigate p-JAK/STAT and VEGF expression. Diabetes was induced by intraperitoneal injection of STZ (50 mg/kg) in C57BL/6 mice for 5 days. DR development was evaluated every 4 weeks. JAK/STAT inhibitors were administered for 8 weeks. Immunofluorescence was used to measure the activation status of the JAK/STAT pathway and VEGF production in the retinal tissue.In ARPE-19 cells exposed to high-glucose conditions, the mRNA and secretory protein levels of VEGF, p-JAK1, p-JAK2, p-STAT3, and p-STAT5 levels were significantly increased. Treatment with JAKiI, tofacitinib, and STAT3i significantly suppressed VEGF to basal levels at both the mRNA and secretory levels in vitro. In STZ-induced mice, retinal vascular leakage, p-JAK1, p-JAK2, p-JAK3, p-STAT3, and VEGF were significantly increased after diabetes induction. Diabetes-induced retinal vascular leakage was significantly reduced by treatment with JAKiI and tofacitinib. Increased p-JAK1 and VEGF in STZ-induced mice were significantly reduced by JAKiI (p 0.05, p 0.001) and tofacitinib (p 0.001, respectively).JAK1 may be more involved in VEGF production and DR progression in mice than JAK2, JAK3, and STAT3. |
| Databáze: | OpenAIRE |
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