Shiroto Yuki, Saga Ryo, Yoshino Hironori, Hosokawa Yoichiro, Isokawa Keitaro, Tsuruga Eichi
Department of Radiation Science, Graduate School of Health Sciences, Hirosaki University, 66-1 Honcho, Hirosaki, Aomori 036-8564, Japan.
Department of Anatomy, Nihon University School of Dentistry, 1-8-13, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Acta Histochem Cytochem. 2021 Feb 25;54(1):1-9. doi: 10.1267/ahc.20-00021. Epub 2021 Feb 9.
The ciliary zonules, also known as the zonules of Zinn, help to control the thickness of the lens during focusing. The ciliary zonules are composed of oxytalan fibers, which are synthesized by human nonpigmented ciliary epithelial cells (HNPCEC). The ciliary zonules are exposed to ultraviolet (UV), especially UV-A and UV-B, throughout life. We previously demonstrated that UV-B, but not UV-A, degrades fibrillin-1- and fibrillin-2-positive oxytalan fibers. However, the mechanism by which UV-B degrades oxytalan fibers remains unknown. In this study, we investigate the involvement of matrix metalloproteinase-2 (MMP-2) in the UV-B-induced degradation of fibrillin-1- and fibrillin-2-positive oxytalan fibers in cultured HNPCECs. Enzyme-linked immunosorbent assay revealed that UV-B irradiation at levels of 100 and 150 mJ/cm significantly increased the level of active MMP-2. Notably, MMP-2 inhibitors completely suppressed the degradation of fibrillin-1- and fibrillin-2-positive oxytalan fibers. In addition, we show that UV-B activates MMP-2 via stress-responsive kinase p38. Taken together, the results suggest that UV-B activates a production of active type of MMP-2 via the p38 pathway, and subsequently, an active-type MMP-2 degrades the fibrillin-1- and fibrillin-2-positive oxytalan fibers in cultured HNPCECs.
睫状小带，也称为秦氏小带，在聚焦过程中有助于控制晶状体的厚度。睫状小带由弹力纤维原纤维组成，这些纤维由人无色素睫状上皮细胞（HNPCEC）合成。睫状小带在一生中都会暴露于紫外线（UV），尤其是UV-A和UV-B。我们之前证明，UV-B而非UV-A会降解原纤维蛋白-1和原纤维蛋白-2阳性的弹力纤维原纤维。然而，UV-B降解弹力纤维原纤维的机制仍然未知。在本研究中，我们调查了基质金属蛋白酶-2（MMP-2）在培养的HNPCEC中UV-B诱导的原纤维蛋白-1和原纤维蛋白-2阳性弹力纤维原纤维降解中的作用。酶联免疫吸附测定显示，100和150 mJ/cm水平的UV-B照射显著增加了活性MMP-2的水平。值得注意的是，MMP-2抑制剂完全抑制了原纤维蛋白-1和原纤维蛋白-2阳性弹力纤维原纤维的降解。此外，我们表明UV-B通过应激反应激酶p38激活MMP-2。综上所述，结果表明UV-B通过p38途径激活活性型MMP-2的产生，随后，活性型MMP-2降解培养的HNPCEC中原纤维蛋白-1和原纤维蛋白-2阳性的弹力纤维原纤维。
