| First Author | Chen X | Year | 2020 |
| Journal | Mol Vis | Volume | 26 |
| Pages | 517-529 | PubMed ID | 32818015 |
| Mgi Jnum | J:310337 | Mgi Id | MGI:6755978 |
| Citation | Chen X, et al. (2020) Interleukin-6 promotes proliferative vitreoretinopathy by inducing epithelial-mesenchymal transition via the JAK1/STAT3 signaling pathway. Mol Vis 26:517-529 |
| abstractText | Purpose: Interleukin-6 (IL-6) is elevated in intraocular fluid from eyes with proliferative vitreoretinopathy (PVR), but the exact role of the cytokine is still unclear. We investigated the function and mechanism of IL-6 in retinal pigment epithelium (RPE) cell biology in vitro and in a mouse model in vivo. Methods: After treatment with various concentrations of IL-6, RPE cell proliferation was assessed with cell counting kit-8 (CCK-8) assay, and epithelial-mesenchymal transition (EMT) markers were evaluated using western blotting and immunofluorescent staining. The activation of JAK1/STAT3 signaling was determined with western blotting. Moreover, the effects of blockade of IL-6/JAK1/STAT3 signaling were investigated using pharmacological inhibitor S3I-201. For in vivo studies, the PVR model was induced with intravitreal injection of dispase/collagenase in wild-type and IL-6 knockout mice. The severity of PVR was evaluated with histological analysis. The expression of IL-6, gp130, and EMT markers was assessed with quantitative real-time PCR and western blotting. Results: IL-6 statistically significantly induced RPE cell proliferation and EMT in a dose-dependent manner in vitro, which was accompanied by rapid phosphorylation of JAK1 and STAT3. Blockade of the IL-6/JAK1/STAT3 pathway with S3I-201 apparently inhibited RPE proliferation and EMT. Furthermore, IL-6 and gp130 overexpression, and JAK1/STAT3 signaling hyperactivation were detected in the retinas of the wild-type mice at 1, 3, and 7 days after dispase/collagenase injection. Finally, we confirmed that IL-6 deficiency markedly alleviated mouse PVR development via inhibiting EMT. Conclusions: These findings indicate that IL-6 promotes PVR by inducing RPE proliferation and EMT via the JAK1/STAT3 signaling pathway. We provided new evidence that therapeutic strategies to block IL-6 may be beneficial for PVR. |
