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白细胞介素-6 促进视网膜色素上皮细胞的迁移和细胞外基质合成。

Interleukin-6 promotes migration and extracellular matrix synthesis in retinal pigment epithelial cells.

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

出版信息

Histochem Cell Biol. 2020 Dec;154(6):629-638. doi: 10.1007/s00418-020-01923-4. Epub 2020 Sep 30.

Abstract

Proliferative vitreoretinopathy (PVR) is the most common cause of surgical failure in the rhegmatogenous retinal detachment (RD) treatment. Retinal pigment epithelial (RPE) cell proliferation, migration, and the synthesis of extracellular matrix (ECM) are intrinsic to the formation of a PVR membrane. High level of interleukin-6 (IL-6) has been found in the vitreous of PVR patients, while the role of IL-6 in RPE cells remaining further characterized. In the present study, we evaluated the potential regulatory effects of IL-6 on cell migration, ECM components, and transforming growth factor β2 (TGF-β2) expression in RPE cells. Furthermore, cell counting kit-8 (CCK‑8) assay was used to investigate cell proliferation activity. We found that IL-6 promoted fibronectin (Fn) and type I collagen (COL-1), TGF-β2 expression in RPE cells, also stimulate RPE cell migration effectively. Moreover, the induction of IL-6 activated the Janus kinase/signal transducers and activators of transcription (JAK/STAT3) and the nuclear factor kappa-B (NF-κB) signaling pathways significantly. Simultaneously, both JAK/STAT3 and NF-κB pathways inhibitors, WP1066 and BAY11-7082, alleviated IL-6-induced biological effects, respectively. However, it was noted that IL-6 had little effect on α-smooth muscle actin (α-SMA) expression. Collectively, our results reveal that IL-6 promotes RPE cell migration and ECM synthesis via activating JAK/STAT3 and NF-κB signaling pathways, which may play a crucial role in PVR formation.

摘要

增生性玻璃体视网膜病变(PVR)是孔源性视网膜脱离(RD)治疗中手术失败的最常见原因。视网膜色素上皮(RPE)细胞的增殖、迁移和细胞外基质(ECM)的合成是 PVR 膜形成的内在过程。在 PVR 患者的玻璃体中发现白细胞介素 6(IL-6)水平较高,而 IL-6 在 RPE 细胞中的作用仍有待进一步研究。在本研究中,我们评估了 IL-6 对 RPE 细胞迁移、ECM 成分和转化生长因子 β2(TGF-β2)表达的潜在调节作用。此外,还使用细胞计数试剂盒-8(CCK-8)测定法研究了细胞增殖活性。我们发现,IL-6 促进了 RPE 细胞中纤维连接蛋白(Fn)和 I 型胶原(COL-1)、TGF-β2 的表达,还能有效刺激 RPE 细胞迁移。此外,IL-6 的诱导激活了 Janus 激酶/信号转导和转录激活因子(JAK/STAT3)和核因子 kappa-B(NF-κB)信号通路。同时,JAK/STAT3 和 NF-κB 通路抑制剂 WP1066 和 BAY11-7082 分别减轻了 IL-6 诱导的生物学效应。然而,值得注意的是,IL-6 对α-平滑肌肌动蛋白(α-SMA)的表达几乎没有影响。综上所述,我们的研究结果表明,IL-6 通过激活 JAK/STAT3 和 NF-κB 信号通路促进 RPE 细胞迁移和 ECM 合成,这可能在 PVR 的形成中起关键作用。

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