TGF-β1 induces lens cells to accumulate α-smooth muscle actin, a marker for subcapsular cataracts

Hales, Angela M.; Schulz, Angela; Chamberlain, Coral G.; McAvoy, John W.

doi:10.3109/02713689409015091

Cited by 150 publications

(79 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…α-SMA is a well known marker of myofibroblast-like cells, and accumulates in tissues characterized by fibrosis or anterior subcapsular cataract, but not in normal tissue [8,28,39,42]. Therefore, in order to examine the role of MMP-2 in the expression of α-SMA, we performed a Western blot analysis.…”

Section: Overexpression Of Mmp-2 Induces Transformation Of Lecsmentioning

confidence: 99%

“…α-SMA is used as a marker for transformed fibrotic cell types in various tissues [30,[36][37][38][39], and is also observed in LECs in pathological conditions [8,40]. Therefore we examined immunoreactivity for α-SMA and MMP-2 in rat lenses incubated with TGF-β " .…”

Section: Presence Of Mmp-2 Within the Anterior Subcapsular Plaques Ofmentioning

confidence: 99%

“…Loss of epithelial polarity and cell multi-layering are well known signs of pathogenesis, especially in oncogenesis, renal dysfunction and catarectogenesis, since alterations in cellular structure lead to cell and organ dysfunction [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells

et al. 2001

View full text Add to dashboard Cite

Section: Overexpression Of Mmp-2 Induces Transformation Of Lecsmentioning

confidence: 99%

Section: Presence Of Mmp-2 Within the Anterior Subcapsular Plaques Ofmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells

et al. 2001

View full text Add to dashboard Cite

“…Numerous studies have shown that inappropriate TGFβ signaling in the eye results in an EMT that bears a morphologic and molecular resemblance to some forms of human cataract, including anterior subcapsular cataract (ASC) and posterior capsular opacification (PCO; 56). Reports of increased levels of TGFβ in many eye diseases (57), together with other studies in vitro and in vivo, have shown that TGFβ-induced EMT of lens epithelial cells results in human ASC phenotypes (57,(58)(59)(60)(61)(62)(63)(64). All report the presence of elongate, spindle-shaped myofibroblastlike cells, as well as lens capsule wrinkling, apoptotic cell death and extensive accumulation of ECM, interspersed between the transdifferentiated cells.…”

Section: Introductionmentioning

confidence: 99%

Sprouty Is a Negative Regulator of Transforming Growth Factor β-Induced Epithelial-to-Mesenchymal Transition and Cataract

Shin

Basson

Robinson

et al. 2012

Mol Med

Self Cite

View full text Add to dashboard Cite

Fibrosis affects an extensive range of organs and is increasingly acknowledged as a major component of many chronic disorders. It is now well accepted that the elevated expression of certain inflammatory cell-derived cytokines, especially transforming growth factor β (TGFβ), is involved in the epithelial-to-mesenchymal transition (EMT) leading to the pathogenesis of a diverse range of fibrotic diseases. In lens, aberrant TGFβ signaling has been shown to induce EMT leading to cataract formation. Sproutys (Sprys) are negative feedback regulators of receptor tyrosine kinase (RTK)-signaling pathways in many vertebrate systems, and in this study we showed that they are important in the murine lens for promoting the lens epithelial cell phenotype. Conditional deletion of Spry1 and Spry2 specifically from the lens leads to an aberrant increase in RTK-mediated extracellular signal-regulated kinase 1/2 phosphorylation and, surprisingly, elevated TGFβ-related signaling in lens epithelial cells, leading to an EMT and subsequent cataract formation. Conversely, increased Spry overexpression in lens cells can suppress not only TGFβ-induced signaling, but also the accompanying EMT and cataract formation. On the basis of these findings, we propose that a better understanding of the relationship between Spry and TGFβ signaling will not only elucidate the etiology of lens pathology, but will also lead to the development of treatments for other fibrotic-related diseases associated with TGFβ-induced EMT.

show abstract

“…In a recent study, TSA was found to suppress proliferation and EMT of lens epithelial cells (LECs) using SRA01/04 and HLEB3 lines. 20 As transdifferentiated LECs show increased expression of αSMA, a marker for subcapsular cataracts and PCO, 3,4,21,22 the current study was designed to study the effect of histone acetylation by TSA on αSMA and the changes that take place at its promoter region during TGF-β-induced EMT of LECs.…”

Section: Introductionmentioning

confidence: 99%

Association of histone acetylation at the ACTA2 promoter region with epithelial mesenchymal transition of lens epithelial cells

Ganatra¹,

Rajkumar²,

Gajjar³

et al. 2015

Eye

View full text Add to dashboard Cite

Purpose Epithelial mesenchymal transition (EMT) plays a central role in the development of fibrotic complications of the lens. The current study is designed to check whether EMT of lens epithelial cells (LECs) is regulated by epigenetic modifications and to evaluate the effect of Trichostatin-A (TSA) on the transforming growth factor-β (TGF-β)-induced EMT. Methods Fetal human LECs (FHL124) were treated with TGF-β2 in the presence or absence of TSA. Levels of mRNA, protein, as well as localization of α-smooth muscle actin (αSMA) were studied along with migration of LECs. Acetylation of histone H4 was analyzed and chromatin immunoprecipitation (ChIP) was carried out to study the level of acetylated histone H4 at the promoter of αSMA gene (ACTA2). Student's t-test was used for statistical analysis. Results TGF-β2 treatment resulted in myofibroblast-like changes and increased migratory capacity of FHL124. Protein and mRNA expression of αSMA increased, and immunofluorescence revealed presence of extensive stress fibers. TSA treatment preserved epithelial morphology, retarded cell migration, and abrogated an increase in αSMA levels. TSA led to the accumulation of acetylated histone H4 that was reduced on TGF-β2 treatment. However, increased level of histone H4 acetylation was found at the ACTA2 promoter region during TGF-β treatment.Conclusions The increased level of αSMA, a hallmark of EMT in LECs, is associated with increased level of histone H4 acetylation at its promoter region, and TSA helps in suppressing EMT by epigenetically reducing this level. TSA thus shows promising potential in management of fibrotic conditions of the lens.

show abstract

TGF-β1 induces lens cells to accumulate α-smooth muscle actin, a marker for subcapsular cataracts

Cited by 150 publications

References 15 publications

Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells

Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells

Sprouty Is a Negative Regulator of Transforming Growth Factor β-Induced Epithelial-to-Mesenchymal Transition and Cataract

Association of histone acetylation at the ACTA2 promoter region with epithelial mesenchymal transition of lens epithelial cells

Contact Info

Product

Resources

About