Interleukin-6 promotes migration and extracellular matrix synthesis in retinal pigment epithelial cells
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ORIGINAL PAPER
Interleukin‑6 promotes migration and extracellular matrix synthesis in retinal pigment epithelial cells Tiantian Qi1 · Ruihua Jing1 · Chan Wen1 · Conghui Hu1 · Yunqing Wang1 · Cheng Pei1 · Bo Ma1 Accepted: 17 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Interleukin-6 · Proliferative vitreoretinopathy · Extracellular matrix synthesis · Migration · JAK/STAT3 signaling pathway · NF-κb signaling pathway
Introduction Proliferative vitreoretinopathy (PVR) is considered as a defective scarring process, causing a formation of the fibrotic membranes within the vitreous cavity and retinal surfaces. It is the most common cause of surgical failure in the rhegmatogenous retinal detachment (RD) treatment (Chiba 2014; Pastor 1998; Pastor et al. 2002). Surgical repair Tiantian Qi and Ruihua Jing contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00418-020-01923-4) contains supplementary material, which is available to authorized users. * Cheng Pei [email protected] * Bo Ma [email protected] 1
Department of Ophthalmology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
of the detached retina is the primary PVR treatment currently. However, it eagerly requires a more precise understanding of PVR mechanics and novel targeted drugs due to the low postoperative satisfaction rate. In PVR, RPE cells were identified as the main participants. As the blood–r
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