β-Catenin/CBP–Dependent Signaling Regulates TGF-β–Induced Epithelial to Mesenchymal Transition of Lens Epithelial Cells

Taiyab, Aftab; Korol, Anna; Deschamps, Paula; West‐Mays, Judith A.

doi:10.1167/iovs.16-20162

Cited by 37 publications

(34 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, the current study in lens epithelial explants demonstrates that the progression of TGFβ-induced demonstrated that β-catenin-mediated signaling, specifically when in complex with CREB-binding protein, is required for TGFβ-induced EMT, outlining a manner in which the effects of EMT are propagated in a feed-forward loop (66). Therefore, our findings demonstrate a …”

Section: Discussionsupporting

confidence: 52%

RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A

Korol

Taiyab

West‐Mays

2016

Mol Med

Self Cite

View full text Add to dashboard Cite

Transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) leads to the formation of ocular fibrotic pathologies, such as anterior subcapsular cataract and posterior capsule opacification. Remodeling of the actin cytoskeleton, mediated by the Rho family of GTPases, plays a key role in EMT. However, how actin dynamics affect downstream markers of EMT has not been fully determined. Our previous work suggests that myocardin-related transcription factor A (MRTF-A), an actin-binding protein, might be an important mediator of TGFβ-induced EMT in lens epithelial cells. The aim of the current study was to determine the requirement of RhoA/ROCK signaling in mediating TGFβ-induced nuclear accumulation of MRTF-A and ultimate expression of α-smooth muscle actin (αSMA), a marker of a contractile myofibroblast phenotype. Using rat lens epithelial explants, we demonstrate that ROCK inhibition using Y-27632 prevents TGFβ-induced nuclear accumulation of MRTF-A, Ecadherin/β-catenin complex disassembly, and αSMA expression. Using a novel inhibitor specifically targeting MRTF-A signaling, CCG-203971, we further demonstrate the requirement of MRTF-A nuclear localization and activity in the induction of αSMA expression. Overall, our findings suggest that TGFβ-induced cytoskeletal reorganization through RhoA/ROCK/MRTF-A signaling is critical to EMT of lens epithelial cells.

show abstract

Section: Discussionsupporting

confidence: 52%

RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A

Korol

Taiyab

West‐Mays

2016

Mol Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…ERK1/2, a type of MAPK, has been implicated as an important component in many signaling systems containing polymethoxylated flavones involved in various biological functions, such as the differentiation and lipolysis of adipocytes, neurotrophic action, and MMP expression. 14,26,27) In lens epithelial cells, ERK1/2 was reported to be involved in the TGFβ-induced EMT 28) ; therefore, 5,7-dimethoxyflavone may inhibit the EMT in TGFβtreated LECs, and lead to the visual impairments observed in ASC and PCO. The relationship between the expression of MMP-9 and the EMT, and the regulation of this by KPMFs, should be investigated further in the future.…”

Section: Discussionmentioning

confidence: 99%

Potential Therapeutic Agents, Polymethoxylated Flavones Isolated from <i>Kaempferia parviflora</i> for Cataract Prevention through Inhibition of Matrix Metalloproteinase-9 in Lens Epithelial Cells

Miyata

Tatsuzaki²,

Yang³

et al. 2019

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Natural flavonoids have powerful antioxidant activity and have been reported to show promising protective effects against cataracts. The plant Kaempferia parviflora (K. parviflora) is indigenous to southeast Asia, including Thailand, and typically contains polymethoxylated flavones. The flavones in K. parviflora are reported to have various biological properties. Recently, polymethoxylated flavones of K. parviflora (KPMFs) were shown to have potent Sirtuin 1 enzyme-stimulating and anti-glycation activities that led to the suppression of cataract formation. Matrix metalloproteinases (MMPs) are upregulated in several pathologic ocular diseases, including cataracts, and have been established as an attractive target for the prevention and/or treatment of specific cataract phenotypes, such as anterior subcapsular cataract (ASC) and posterior capsular opacification (PCO). In the present study, we investigated the effect of KPMFs on MMP (gelatinase) activity in the human lens epithelial cell line, SRA01/04. We demonstrated that KPMFs inhibited the phorbol ester-induced MMP-9 activity and the mRNA expression through the suppression of mitogen-activated protein kinases (MAPKs) phosphorylation in human lens epithelial cells; 5,7-dimethoxyflavone was found to exert the most potent inhibition, but 3,5,7,4′-tetramethoxyflavone and 3,5,7,3′,4′-pentamethoxyflavone also resulted in considerable inhibition. Our results suggested that the consumption of PMFs isolated from K. parviflora, may be an effective strategy to delay the development of cataracts, such as ASC and PCO.

show abstract

“…At first, β-elemene (Sigma-Aldrich, St. Louis, MO) was tested for its independent effects at six doses (5,10,20,40,80, and 160 μg/ml) for 24 h and 48 h. The phosphotidylinsitol-3-kinase (PI3K) inhibitor LY294002 (Sigma) and protein kinase B (Akt) inhibitor MK2206 (Sigma) were dissolved in dimethyl sulfoxide. The working concentrations of LY294002 and MK2206 were 10 μM and 1 μM, respectively, as previously described [29][30][31]. With or without pretreatment with the above inhibitors for 1 h, VSC4.1 motor neurons were exposed to β-elemene (20 μg/ml) for 24 h. Chemical hypoxic injury of VSC4.1 motor neurons was then induced by CoCl 2 (Sigma) in a dose-dependent manner (150, 300, 400, 500, 600, and 1200 μM) for 24 h. Then, VSC4.1 motor neurons were pretreated with 20 μg/ml β-elemene for 4 h to observe its protective effects on CoCl 2 (400, 500, and 600 μM)-induced cellular damage.…”

Section: Methodsmentioning

confidence: 99%

Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury

Wang

Ren

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract β-elemene in vitro and in a rat model of SCI. Methods: CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen’s method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression. Results: β-elemene (20 μg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. β-elemene reduced CoCl₂-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that β-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that β-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, β-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1β. Conclusion: β-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, β-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of β-elemene in SCI patients.

show abstract

β-Catenin/CBP–Dependent Signaling Regulates TGF-β–Induced Epithelial to Mesenchymal Transition of Lens Epithelial Cells

Cited by 37 publications

References 59 publications

RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A

RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A

Potential Therapeutic Agents, Polymethoxylated Flavones Isolated from <i>Kaempferia parviflora</i> for Cataract Prevention through Inhibition of Matrix Metalloproteinase-9 in Lens Epithelial Cells

Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury

Contact Info

Product

Resources

About