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

Nahomi, Rooban B.; Pantcheva, Mina B.; Nagaraj, Ram H.

doi:10.1042/bcj20160128

Cited by 25 publications

(33 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations suggest that the acetylation of Smads may not have contributed to the inhibition of TGFβ2-mediated EMT by aspirin. The downregulation of αB-crystallin by aspirin could have also contributed to the inhibition of EMT, as we have previously shown that αB-crystallin binds to Smads and Snail and translocates to the nucleus during the TGFβ2-mediated EMT of LECs [42]. Such binding could have stabilized the transcription factors and allowed them to bind to DNA and promote EMT.…”

Section: Discussionmentioning

confidence: 93%

“…Lensectomy in mice was performed as previously described [42]. In the case of mice (strain 129/Sv, 12-week-old males) receiving aspirin, the animals were orally administered 1 mg/ml aspirin or 0.89 mg/ml sodium salicylic acid (SA, molar equivalent to aspirin) in 25 mM sodium phosphate-buffered (SPB, pH 7.4) drinking water for 5 days prior to the lensectomy and for 5 days after the procedure.…”

Section: Effect Of Aspirin On the Emt Of Lecs In Lensectomized Micementioning

confidence: 99%

See 1 more Smart Citation

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3

Nam

Smith

Pantcheva

et al. 2020

Biochemical Journal

View full text Add to dashboard Cite

Posterior capsule opacification (PCO) is a complication after cataract surgery that can disrupt vision. The epithelial to mesenchymal transition (EMT) of lens epithelial cells (LECs) in response to transforming growth factor β2 (TGFβ2) has been considered an obligatory mechanism for PCO. In this study, we tested the efficacy of aspirin in inhibiting the TGFβ2-mediated EMT of human LECs, LECs in human lens capsular bags, and lensectomized mice. In human LECs, the levels of the EMT markers α-smooth muscle actin (α-SMA) and fibronectin were drastically reduced by treatment with 2 mM aspirin. Aspirin also halted the EMT response of TGFβ2 when introduced after EMT initiation. In human capsular bags, treatment with 2 mM aspirin significantly suppressed posterior capsule wrinkling and the expression α-SMA in capsule-adherent LECs. The inhibition of TGFβ2-mediated EMT in human LECs was not dependent on Smad phosphorylation or MAPK and AKT-mediated signaling. We found that aspirin significantly increased the acetylation of K56 and K122 in histone H3 of human LECs. Chromatin immunoprecipitation assays using acetyl-H3K56 or acetyl-H3K122 antibody revealed that aspirin blocked the TGFβ2-induced acetylation of H3K56 and H3K122 at the promoter regions of ACTA2 and COL1A1. After lensectomy in mice, we observed an increase in the proliferation and α-SMA expression of the capsule-adherent LECs, which was ameliorated by aspirin administration through drinking water. Taken together, our results showed that aspirin inhibits TGFβ2-mediated EMT of LECs, possibly from epigenetic down-regulation of EMT-related genes.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Effect Of Aspirin On the Emt Of Lecs In Lensectomized Micementioning

confidence: 99%

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3

Nam

Smith

Pantcheva

et al. 2020

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Functional enrichment analysis with StarBase software identified 17 pathways [51]. Of them, the TGF-beta signalling pathway and IGF1/PIK3/AKT signalling pathway might be correlated to the pathogenesis of ARC [16,47,52]. LncRNA XLOC_046118|n371509, which belongs to the lncRNA XIST family, was up-regulated in nuclear ARC compared to transparent lens capsules.…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

Liu

Shan

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Age-related cataract (ARC) remains the leading cause of visual impairment among the elderly population. Long non-coding RNAs (lncRNAs) have emerged as potential regulators in many ocular diseases. However, the role of lncRNAs in nuclear ARC, a subtype of ARC, requires further elucidation. Methods: LncRNA sequencing was performed to identify differentially expressed lncRNAs between the capsules of transparent and nuclear ARC lenses. Expression validation was confirmed by qRT-PCR. MTT assay, Calcein-AM and propidium iodide double staining, Rhodamine 123 and Hoechst double staining, EdU and transwell assay were used to determine the role of H19 or miR-675 in the viability, apoptosis, proliferation and migration of primary cultured human lens epithelial cells (HLECs). Bioinformatics and luciferase reporter assays were used to identify the binding target of miR-675. Results: Sixty-three lncRNAs are differentially expressed between the capsules of transparent and nuclear ARC lenses. One top abundantly expressed lncRNA, H19, is significantly up-regulated in the nuclear ARC lens capsules and positively associated with nuclear ARC grade. H19 knockdown accelerates apoptosis development and reduces the proliferation and migration of HLECs upon oxidative stress. H19 is the precursor of miR-675, and a reduction of H19 inhibits miR-675 expression. miR-675 regulates CRYAA expression by targeting the binding site within the 3’UTR. Moreover, miR-675 increases the proliferation and migration while decreasing the apoptosis of HLECs upon oxidative stress. Conclusion: H19 regulates HLECs function through miR-675-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of nuclear ARC.

show abstract

“…In previous studies we showed that aldose reductase (AR) can play a role in the TGF-β-mediated EMT response through interactions the Smad protein family of signaling proteins [9]. In a similar manner, Nahomi and colleagues showed that αB-crystallin plays an essential role for the TGF-β2-mediated EMT of LECs [10]. …”

Section: Introductionmentioning

confidence: 99%

Influence of aldose reductase on epithelial-to-mesenchymal transition signaling in lens epithelial cells

Chang

Shieh

Petrash

2017

Chemico-Biological Interactions

View full text Add to dashboard Cite

Cataract is the most frequent cause of blindness worldwide and is treated by surgical removal of the opaque lens to restore the light path to the retina. While cataract surgery is a safe procedure, some patients develop a complication of the surgery involving opacification and wrinkling of the posterior lens capsule. This process, called posterior capsule opacification (PCO), requires a second clinical treatment that can in turn lead to additional complications. Prevention of PCO is a current unmet need in the vision care enterprise. The pathogenesis of PCO involves the transition of lens epithelial cells to a mesenchymal phenotype, designated epithelial-to-mesenchymal transition (EMT). Our previous studies showed that transgenic mice designed for overexpression of human aldose reductase developed lens defects reminiscent of PCO. In the current study, we evaluated the impact of aldose reductase (AR) on expression of expression of EMT markers in the lens. Primary lens epithelial cells from AR-transgenic mice showed downregulated expression of Foxe3 and Pax6 and increased expression of α-SMA, fibronectin and snail, a pattern of gene expression typical of cells undergoing EMT. A role for AR in these changes was further confirmed when we observed that they could be normalized by treatment of cells with Sorbinil, an AR inhibitor. Smad-dependent and Smad-independent pathways are known to contribute to EMT. Interestingly, AR overexpression induced ERK but not Smad-2 activation. These results suggest that elevation of AR may lead to activation of ERK signaling and thus play a role in TGF-β/Smad independent induction of EMT in lens epithelial cells.

show abstract

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

Cited by 25 publications

References 43 publications

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

Influence of aldose reductase on epithelial-to-mesenchymal transition signaling in lens epithelial cells

Contact Info

Product

Resources

About