Institute of Laboratory Animal Science, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Institute of Laboratory Animal Science, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; College of Tourism and Culinary Science, Yangzhou University, Yangzhou, Jiangsu, China; College of Life Sciences, Anhui Agricultural University, Hefei, Anhui, China.
Biochem Biophys Res Commun. 2020 Aug 20;529(2):487-493. doi: 10.1016/j.bbrc.2020.06.026. Epub 2020 Jul 2.
Protein phosphatase 5 (PP5) plays an important role in cell proliferation, differentiation, and development. Transgenic PP5 mice (Tg-hPP5 mice) overexpressing human PP5 gene were successfully generated by embryo injection. Tg-hPP5 mice spontaneously developed corneal hyperplasia and ocular surface squamous neoplasia (OSSN). To investigate the mechanism behind PP5-induced corneal hyperplasia, we performed immunohistochemistry, quantitative real-time PCR, and Western Blotting analyses on the corneas of Tg-hPP5 mice at 2 months and 9 months of age. We provide the first demonstration that Tg-hPP5 mice develop corneal hyperplasia at 9-months of age demonstrated via histological analysis and in vitro co-transfection investigation. We also present data that the expression of p53 is significantly reduced while the expression of FGF-7 is significantly increased in Tg-hPP5 mice with corneal hyperplasia. Co-transfection of PP5, p53, and FGF-7-promoter-driven luciferase revealed that PP5 promotes while p53 inhibits FGF-7 expression, which indicates PP5 overexpression inhibits p53 phosphorylation, thereby reducing its tumor suppressor function and increasing FGF-7 expression. In conclusion, PP5 plays a pivotal role in corneal hyperplasia development and its downregulation is a potential target for corneal hyperplasia and OSSN treatment.
蛋白磷酸酶 5（PP5）在细胞增殖、分化和发育中发挥重要作用。通过胚胎注射成功地生成了过表达人 PP5 基因的转基因 PP5 小鼠（Tg-hPP5 小鼠）。Tg-hPP5 小鼠自发地发展出角膜增生和眼表面鳞状肿瘤（OSSN）。为了研究 PP5 诱导的角膜增生的机制，我们对 2 个月和 9 个月大的 Tg-hPP5 小鼠的角膜进行了免疫组织化学、定量实时 PCR 和 Western Blotting 分析。我们首次证明，通过组织学分析和体外共转染研究，Tg-hPP5 小鼠在 9 个月大时会发生角膜增生。我们还提供的数据表明，在发生角膜增生的 Tg-hPP5 小鼠中，p53 的表达显著降低，而 FGF-7 的表达显著增加。PP5、p53 和 FGF-7 启动子驱动的荧光素酶的共转染表明，PP5 促进而 p53 抑制 FGF-7 的表达，这表明 PP5 过表达抑制 p53 的磷酸化，从而降低其肿瘤抑制功能并增加 FGF-7 的表达。总之，PP5 在角膜增生的发展中起着关键作用，其下调可能是角膜增生和 OSSN 治疗的一个潜在靶点。
