scholarly journals Aldose Reductase Mediates Transforming Growth Factor β2 (TGF-β2)–Induced Migration and Epithelial-To-Mesenchymal Transition of Lens-Derived Epithelial Cells

2015 ◽  
Vol 56 (8) ◽  
pp. 4198 ◽  
Author(s):  
Kun-Che Chang ◽  
J. Mark Petrash
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Aldose Reductase ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Mesenchymal Transition ◽  
Transforming Growth Factor Β2

Transforming growth factor-β2-mediated mesenchymal transition in lens epithelial cells is repressed in the absence of RAGE

2021 ◽  
Vol 478 (12) ◽  
pp. 2285-2296
Author(s):  
Mi-Hyun Nam ◽  
Mina B. Pantcheva ◽  
Johanna Rankenberg ◽  
Ram H. Nagaraj
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Knockout Mice ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Lens Epithelial Cells ◽  
Wild Type ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Transforming Growth Factor Β2

Transforming growth factor-β2 (TGFβ2)-mediated epithelial to mesenchymal transition (EMT) in lens epithelial cells (LECs) has been implicated in fibrosis associated with secondary cataracts. In this study, we investigated whether the receptor for advanced glycation end products (RAGE) plays a role in TGFβ2-mediated EMT in LECs. Unlike in the LECs from wild-type mice, TGFβ2 failed to elicit an EMT response in LECs from RAGE knockout mice. The lack of RAGE also diminished TGFβ2-mediated Smad signaling. In addition, treatment with TGFβ2 increased IL-6 levels in LECs from wild-type mice but not in those from RAGE knockout mice. Treatment of human LECs with the RAGE inhibitor FPS-ZM1 reduced TGFβ2-mediated Smad signaling and the EMT response. Unlike that in wild-type lenses, the removal of fiber cell tissue in RAGE knockout lenses did not result in elevated levels of α-smooth muscle actin (α-SMA), fibronectin (FN), and integrin β1 in capsule-adherent LECs. Taken together, these results suggest that TGFβ2 signaling is intricately linked to RAGE. Targeting RAGE could be explored as a therapeutic strategy against secondary cataracts.

scholarly journals Scleraxis regulates Twist1 and Snai1 expression in the epithelial-to-mesenchymal transition

2018 ◽  
Vol 315 (3) ◽  
pp. H658-H668 ◽  
Author(s):  
Danah S. Al-Hattab ◽  
Hamza A. Safi ◽  
Raghu S. Nagalingam ◽  
Rushita A. Bagchi ◽  
Matthew T. Stecy ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Cardiac Development ◽  
Cardiac Fibroblasts ◽  
Transforming Growth Factor Β ◽  
Mesenchymal Transition ◽  
E Cadherin

Numerous physiological and pathological events, from organ development to cancer and fibrosis, are characterized by an epithelial-to-mesenchymal transition (EMT), whereby adherent epithelial cells convert to migratory mesenchymal cells. During cardiac development, proepicardial organ epithelial cells undergo EMT to generate fibroblasts. Subsequent stress or damage induces further phenotype conversion of fibroblasts to myofibroblasts, causing fibrosis via synthesis of an excessive extracellular matrix. We have previously shown that the transcription factor scleraxis is both sufficient and necessary for the conversion of cardiac fibroblasts to myofibroblasts and found that scleraxis knockout reduced cardiac fibroblast numbers by 50%, possibly via EMT attenuation. Scleraxis induced expression of the EMT transcriptional regulators Twist1 and Snai1 via an unknown mechanism. Here, we report that scleraxis binds to E-box consensus sequences within the Twist1 and Snai1 promoters to transactivate these genes directly. Scleraxis upregulates expression of both genes in A549 epithelial cells and in cardiac myofibroblasts. Transforming growth factor-β induces EMT, fibrosis, and scleraxis expression, and we found that transforming growth factor-β-mediated upregulation of Twist1 and Snai1 completely depends on the presence of scleraxis. Snai1 knockdown upregulated the epithelial marker E-cadherin; however, this effect was lost after scleraxis overexpression, suggesting that scleraxis may repress E-cadherin expression. Together, these results indicate that scleraxis can regulate EMT via direct transactivation of the Twist1 and Snai1 genes. Given the role of scleraxis in also driving the myofibroblast phenotype, scleraxis appears to be a critical controller of fibroblast genesis and fate in the myocardium and thus may play key roles in wound healing and fibrosis. NEW & NOTEWORTHY The molecular mechanism by which the transcription factor scleraxis mediates Twist1 and Snai1 gene expression was determined. These results reveal a novel means of transcriptional regulation of epithelial-to-mesenchymal transition and demonstrate that transforming growth factor-β-mediated epithelial-to-mesenchymal transition is dependent on scleraxis, providing a potential target for controlling this process.

scholarly journals αB-crystallin is essential for the TGF-β2-mediated epithelial to mesenchymal transition of lens epithelial cells

2016 ◽  
Vol 473 (10) ◽  
pp. 1455-1469 ◽  
Author(s):  
Rooban B. Nahomi ◽  
Mina B. Pantcheva ◽  
Ram H. Nagaraj
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Therapeutic Target ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Lens Epithelial Cell ◽  
Lens Epithelial Cells ◽  
Mesenchymal Transition ◽  
Αb Crystallin

We found that αB-crystallin promoted transforming growth factor (TGF)-β2-induced epithelial to mesenchymal transition (EMT) in lens epithelial cell (LEC) and its depletion resulted in reduced EMT in cultured LEC and in lensectomized mice. αB-Crystallin could be a therapeutic target to block secondary cataract.

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