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Matrix Metalloproteinase-2 Activated by Ultraviolet-B Degrades Human Ciliary Zonules In Vitro
Acta Histochemica et Cytochemica ( IF 1.6 ) Pub Date : 2021-02-25 , DOI: 10.1267/ahc.20-00021
Yuki Shiroto 1 , Ryo Saga 1 , Hironori Yoshino 1 , Yoichiro Hosokawa 1 , Keitaro Isokawa 2 , Eichi Tsuruga 1
Affiliation  

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/cm2 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.



中文翻译:

紫外线-B激活的基质金属蛋白酶-2体外降解人睫状小带。

睫状小带,也称为Zinn小带,在聚焦过程中有助于控制晶状体的厚度。睫状小带由羟talan纤维组成,由人无色素的睫状上皮细胞(HNPCEC)合成。睫状小带终生都暴露于紫外线(UV),尤其是UV-A和UV-B。先前我们证明了UV-B而不是UV-A可以降解原纤维蛋白1和原纤维蛋白2阳性的氧化金属纤维。但是,UV-B降解羟戊烷纤维的机理仍然未知。在这项研究中,我们调查了基质金属蛋白酶2(MMP-2)在培养的HNPCECs中由UV-B诱导的原纤维蛋白1和原纤维蛋白2阳性羟基金属纤维降解的影响。酶联免疫吸附试验表明,UV-B辐射的水平为100和150 mJ / cm 2显着增加了活跃的MMP-2水平。值得注意的是,MMP-2抑制剂可完全抑制纤丝蛋白1和纤丝蛋白2阳性的氧化金属纤维的降解。另外,我们表明,UV-B通过应激反应激酶p38激活MMP-2。两者合计,结果表明,UV-B通过p38途径激活了活性型MMP-2的产生,随后,活性型MMP-2降解了纤维原蛋白1和原纤维蛋白2阳性的oxytalan纤维。培养的HNPCEC。

更新日期:2021-03-17
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