Snail Involves in the Transforming Growth Factor β1-Mediated Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells

Abstract

BackgroundThe proliferation of retinal pigment epithelium (RPE) cells resulting from an epithelial-mesenchymal transition (EMT) plays a key role in proliferative vitreoretinopathy (PVR), which leads to complex retinal detachment and the loss of vision. Genes of Snail family encode the zinc finger transcription factors that have been reported to be essential in EMT during embryonic development and cancer metastasis. However, the function of Snail in RPE cells undergoing EMT is largely unknown.Principal FindingsTransforming growth factor beta(TGF-β)-1 resulted in EMT in human RPE cells (ARPE-19), which was characterized by the expected decrease in E-cadherin and Zona occludin-1(ZO-1) expression, and the increase in fibronectin and α-smooth muscle actin (α-SMA) expression, as well as the associated increase of Snail expression at both mRNA and protein levels. Furthermore, TGF-β1 treatment caused a significant change in ARPE-19 cells morphology, with transition from a typical epithelial morphology to mesenchymal spindle-shaped. More interestingly, Snail silencing significantly attenuated TGF-β1-induced EMT in ARPE-19 cells by decreasing the mesenchymal markers fibronectin and a-SMA and increasing the epithelial marker E-cadherin and ZO-1. Snail knockdown could effectively suppress ARPE-19 cell migration. Finally, Snail was activated in epiretinal membranes from PVR patients. Taken together, Snail plays very important roles in TGF-β-1-induced EMT in human RPE cells and may contribute to the development of PVR.SignificanceSnail transcription factor plays a critical role in TGF-β1-induced EMT in human RPE cells, which provides deep insight into the pathogenesis of human PVR disease. The specific inhibition of Snail may provide a new approach to treat and prevent PVR.

Secretion Profile of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium During Wound Healing

“…[27][28][29][30] However, most in vitro studies used exogenously applied TGFb to activate cellular pathways leading to EMT. 24,[31][32][33] Assays conducted in the current study were performed without addition of exogenous TGFb, yet the cells were able to respond to wounding by activating EMT. The three TGFb isoforms encoded by the human genome 34 have distinct and overlapping functions during wound healing.…”

Estrogen-related receptor α participates transforming growth factor-β (TGF-β) induced epithelial-mesenchymal transition of osteosarcoma cells

“…15 In support of our results, several reports demonstrated that Snail knockdown reverts TGF-b-induced EMT and cell migration in cancer cells. 17,25 TGF-b signals have been suggested to cross talk with estrogenic signal pathways during the tumorigenesis and development of cancers. 2,13 Our present study revealed for the first time that TGF-b treatment can increase the expression and nuclear translocation of ERRa in osteosarcoma cells, while not affect other molecules including ERa, ERb, and ERRg.…”

Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway

“…Snail, a negative regulator of E-cadherin, is one of the key transcription factors promoting EMT (32). Furthermore, the mesenchymal markers MMP9 and α-SMA have been particularly associated with tumor progression and metastatic dissemination in different human cancers (33,34). Here, we demonstrated that GPC3 promoted tumor metastasis through the induction of EMT and could potentially be used as a biomarker.…”