The roles of aV integrins in lens EMT and posterior capsular opacification

被引:73
作者
Mamuya, Fahmy A. [1 ]
Wang, Yan [1 ]
Roop, Victoria H. [1 ]
Scheiblin, David A. [1 ]
Zajac, Jocelyn C. [1 ]
Duncan, Melinda K. [1 ]
机构
[1] Univ Delaware, Dept Biol Sci, Newark, DE USA
关键词
lens; epithelial-to-mesenchymal transition; posterior capsular opacification; integrins; transforming growth factor beta; wound healing response; fibrosis; secondary cataract; EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR-BETA; ACTIVATES LATENT TGF-BETA-1; ALPHA-V INTEGRINS; EXPRESSION; CELLS; CATARACT; MICRORNA; MIR-31; BETA-1-INTEGRIN;
D O I
10.1111/jcmm.12213
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Posterior capsular opacification (PCO) is the major complication arising after cataract treatment. PCO occurs when the lens epithelial cells remaining following surgery (LCs) undergo a wound healing response producing a mixture of -smooth muscle actin (-SMA)-expressing myofibroblasts and lens fibre cells, which impair vision. Prior investigations have proposed that integrins play a central role in PCO and we found that, in a mouse fibre cell removal model of cataract surgery, expression of (V) integrin and its interacting -subunits 1, 5, 6, 8 are up-regulated concomitant with -SMA in LCs following surgery. To test the hypothesis that (V) integrins are functionally important in PCO pathogenesis, we created mice lacking the (V) integrin subunit in all lens cells. Adult lenses lacking (V) integrins are transparent and show no apparent morphological abnormalities when compared with control lenses. However, following surgical fibre cell removal, the LCs in control eyes increased cell proliferation, and up-regulated the expression of -SMA, 1-integrin, fibronectin, tenascin-C and transforming growth factor beta (TGF-)-induced protein within 48hrs, while LCs lacking (V) integrins exhibited much less cell proliferation and little to no up-regulation of any of the fibrotic markers tested. This effect appears to result from the known roles of (V) integrins in latent TGF- activation as (V) integrin null lenses do not exhibit detectable SMAD-3 phosphorylation after surgery, while this occurs robustly in control lenses, consistent with the known roles for TGF- in fibrotic PCO. These data suggest that therapeutics antagonizing (V) integrin function could be used to prevent fibrotic PCO following cataract surgery.
引用
收藏
页码:656 / 670
页数:15
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