Aspirin inhibits TGFß2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3.
Biochem J
; 477(1): 75-97, 2020 01 17.
Article
in En
| MEDLINE
| ID: mdl-31815277
ABSTRACT
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 ß2 (TGFß2) has been considered an obligatory mechanism for PCO. In this study, we tested the efficacy of aspirin in inhibiting the TGFß2-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 2â
mM aspirin. Aspirin also halted the EMT response of TGFß2 when introduced after EMT initiation. In human capsular bags, treatment with 2â
mM aspirin significantly suppressed posterior capsule wrinkling and the expression α-SMA in capsule-adherent LECs. The inhibition of TGFß2-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 TGFß2-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 TGFß2-mediated EMT of LECs, possibly from epigenetic down-regulation of EMT-related genes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histones
/
Anti-Inflammatory Agents, Non-Steroidal
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Aspirin
/
Epithelial Cells
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Posterior Capsule of the Lens
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Capsule Opacification
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Epithelial-Mesenchymal Transition
Limits:
Animals
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Humans
/
Male
Language:
En
Journal:
Biochem J
Year:
2020
Type:
Article
Affiliation country:
United States