GSK3β attenuates TGF-β1 induced epithelial-mesenchymal transition and metabolic alterations in ARPE-19 cells.
While TGF-β1 is known to induce epithelial-mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-β1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-β1 inhibited GSK-3β by accelerating phosphorylation at ser9. GSK-3β inhibitor or knockdown of GSK-3β resulted in enhanced TGF-β1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3β overexpression and PI3K/AKT inhibitor. Importantly, GSK-3β also mediated metabolic reprogramming in TGF-β1-treated cells. Our results indicate that GSK-3β plays a pivotal role in TGF-β1-mediated EMT in ARPE-19 cells.
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
Li
L
Huang
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
Cheng
C
Zhang
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China. Electronic address: sujilin@163.com.
Li
L
Su
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China; Shanghai Xinshijie Eye Hospital, Shanghai 200071, China. Electronic address: rockersong@hotmail.com.
Zhengyu
Z
Song
D000199:Actins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D055442:Metabolome / Q000235:genetics; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D025341:Principal Component Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; C568985:OCLN protein, human; D062793:Occludin; C569042:TJP1 protein, human; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D062826:Zonula Occludens-1 Protein; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
ARPE-19 cells; Epithelial–mesenchymal transition; Glycogen synthase kinase 3β; Metabolomics; Transforming growth factor-β