NFκB-Mediated Expression of Phosphoinositide 3-Kinase δ Is Critical for Mesenchymal Transition in Retinal Pigment Epithelial Cells
Year: 2023
Type: article
Abstract: Epithelial mesenchymal transition (EMT) plays a vital role in a variety of human diseases including proliferative vitreoretinopathy (PVR), in which retinal pigment epithelial (RPE) cells play a key part. Transcriptomic analysis showed that the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was up-regulated in human RPE cells upon treatment with transforming growth factor (TGF)-β2, a multifunctional cytokine associated with clinical PVR. Stimulation of human RPE cells with TGF-β2 induced expression of p110δ (the catalytic subunit of PI3Kδ) and activation of NFκB/p65. CRISPR-Cas9-mediated depletion of p110δ or NFκB/p65 suppressed TGF-β2-induced fibronectin expression and activation of Akt as well as migration of these cells. Intriguingly, abrogating expression of NFκB/p65 also blocked TGF-β2-induced expression of p110δ, and luciferase reporter assay indicated that TGF-β2 induced NFκB/p65 binding to the promoter of the PIK3CD that encodes p110δ. These data reveal that NFκB/p65-mediated expression of PI3Kδ is essential in human RPE cells for TGF-β2-induced EMT, uncovering hindrance of TGF-β2-induced expression of p110δ as a novel approach to inhibit PVR.
Source: Cells
Authors: Haote Han, Yanhui Yang, Zhuo Han, Luping Wang, Lijun Dong, Hui Qi, Bing Liu, Jingkui Tian, Bart Vanhaesebroeck, Andrius Kazlauskas, Guoming Zhang, Shaochong Zhang, Hetian Lei
Institutions: Massachusetts Eye and Ear Infirmary, Harvard University, Zhejiang Cancer Hospital, University of Chinese Academy of Sciences, Ningxia Medical University, Jinan University, Guangzhou Women and Children Medical Center, Guangzhou Medical University, University College London, University of Illinois Chicago
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,669
OpenAlex ID: W4313583358