NFκB-Mediated Expression of Phosphoinositide 3-Kinase δ Is Critical for Mesenchymal Transition in Retinal Pigment Epithelial Cells.
Haote HanYanhui YangZhuo HanLuping WangLijun DongHui QiBing LiuJingkui TianBart VanhaesebroeckAndrius KazlauskasGuoming ZhangShaochong ZhangHetian LeiPublished in: Cells (2023)
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.
Keyphrases
- signaling pathway
- transforming growth factor
- epithelial mesenchymal transition
- induced apoptosis
- pi k akt
- cell cycle arrest
- poor prognosis
- high glucose
- endothelial cells
- diabetic rats
- crispr cas
- oxidative stress
- cell proliferation
- lps induced
- drug induced
- stem cells
- endoplasmic reticulum stress
- cell death
- induced pluripotent stem cells
- inflammatory response
- drug delivery
- artificial intelligence
- gene expression
- electronic health record
- genome wide
- high throughput
- dna methylation
- tyrosine kinase
- genome editing
- machine learning
- big data
- data analysis