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Shizuya Saika, Takeshi Miyamoto, Sai-ichi Tanaka, Takeshi Tanaka, Iku Ishida, Yoshitaka Ohnishi, Akira Ooshima, Toshiyuki Ishiwata, Goro Asano, Tai-ichiro Chikama, Atsushi Shiraishi, Chia-Yang Liu, Candace W.-C. Kao, Winston W.-Y. Kao; Response of Lens Epithelial Cells to Injury: Role of Lumican in Epithelial-Mesenchymal Transition. Invest. Ophthalmol. Vis. Sci. 2003;44(5):2094-2102. doi: 10.1167/iovs.02-1059.
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purpose. Lens epithelial cells (LECs) undergo epithelial-mesenchcymal transition (EMT) after injury and transform into myofibroblasts positive for α-smooth muscle actin (αSMA), an established marker of this process. Lumican is a keratan sulfate proteoglycan core protein. This study was conducted to examine whether human and mouse LECs express lumican after injury. To determine whether lumican may modulate EMT of LECs in response to injury or to exposure to transforming growth factor-β2 (TGFβ2), αSMA expression by the LECs was examined in lumican (Lum)-knockout mice in vivo and in organ culture.
methods. Human postoperative capsular specimens and healing, injured mouse lenses at various intervals were immunostained for lumican or αSMA. αSMA was also immunolocalized in healing, injured lenses of Lum-knockout mice. Finally, expression of lumican and αSMA was examined in lenses of Lum-knockout mice incubated with TGFβ2.
results. Lumican was immunolocalized in matrix in human postoperative capsular opacification. Lumican and αSMA were upregulated in mouse LECs from 8 hours and day 5 after an injury, respectively. LECs accumulated adjacent to the capsular break were of epithelial shape in Lum −/− mice and fibroblast-like in Lum +/− mice during healing. αSMA expression by LECs was significantly delayed in Lum −/− mice, indicating that lumican may modulate injury-induced EMT in LECs. TGFβ2-induced EMT appeared to be suppressed in organ-cultured lenses of Lum −/− mice compared with those of Lum +/+ mice.
conclusions. Human capsular opacification contains lumican, and mouse LECs upregulate lumican and αSMA in response to injury. Loss of lumican perturbs EMT of mouse LECs.
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