July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Regulation of TGF-β mediated epithelial-mesenchymal transition of lens epithelial cells by c-src kinase at high glucose concentration
Author Affiliations & Notes
  • Jian Zhou
    Department of Ophthalmology, Xijing Hospital , Xi'an, Shaanxi, China
  • Footnotes
    Commercial Relationships   Jian Zhou, None
  • Footnotes
    Support  National Natural Science Foundation of China (No.81370998), New Century Excellent Talents Program(NCET-06-932), Innovation science and technology project of Shaanxi province(No.2012KTCQ03-03)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5637. doi:
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      Jian Zhou; Regulation of TGF-β mediated epithelial-mesenchymal transition of lens epithelial cells by c-src kinase at high glucose concentration
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):5637.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Recent studies reported that high dose of glucose contributed to acceleration of renal cell apoptosis and renal fibrosis by inducing epithelial-mesenchymal transition (EMT) of tubular epithelial cells, in which c-Src kinase and TGF-β are key modulators. In the present study, we investigate the roles and relationship of c-Src kinase and TGF-β in EMT of lens epithelial cells (LECs)under high glucose condition.

Methods : Lens epithelial cells-B3 were cultured with high glucose (35.5 mM) in DMEM, in addition with 10 μmol/L PP1 (an inhibitor of c-Src) or 10 μmol/L SB431542 (an inhibitor of ALK5) for 12 hours. In c-Src knockdown experiments, LECs were transfected with shRNA-Vector or shRNA-c-Src and then cultured in DMEM with high glucose for 12 h. Western blot assay was used to evaluate the expressions of c-Src phosphorylation (p-Src418), TGF-β, EMT protein markers (E-cadherin and α-SMA) and ALK5. ELISA assay was used to evaluate the secretion of TGF-β of LECs.

Results : PP1 inhibited the activities of c-Src, activin-like kinase5 (ALK5) and secretion of TGF-β, while SB431542 only down regulated the protein expression and secretion of TGF-β. They all suppressed the EMT of the LECs induced by high glucose. In LEC-B3 of c-Src knockdown, the expressions of p-Src418, ALK5, and TGF-β decreased significantly (p < 0.05), the secretion of TGF-β also suppressed and EMT decreased.

Conclusions : These results suggest that both c-Src and TGF-β promote EMT of LECs under high glucose conditions, with c-Src as the upstream regulatory molecule. Thus, the signal axis of c-Src/TGF-β in EMT of LECs may be a potential novel therapeutic target for the prevention of diabetic subcapsular cataract.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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