Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway
Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway
复制标题
Agrin 通过 Hippo-Yap 信号通路促进角膜缘干细胞增殖和角膜伤口愈合
DOI：
10.1167/iovs.61.5.7
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发表时间：
2020-05-01
影响因子：
4.4
通讯作者：
Huang, Yifei
中科院分区：
文献类型：
--
作者：
Hou, Lulu;Fu, Wenbin;Huang, Yifei
目的探讨Agrin对角膜缘干细胞增殖和角膜创伤愈合的影响及其机制。方法分离培养角膜缘干细胞，用不同浓度的Agrin处理。CCK-8和细胞增殖标志物（Ki 67和pH 3）检测角膜缘干细胞的细胞数量或增殖能力。采用中央角膜上皮清创法建立角膜上皮损伤模型，观察Agrin对角膜缘干细胞增殖及角膜上皮损伤愈合率的影响。结果Agrin促进体外培养的角膜缘干细胞增殖，并增加p63 α的表达，而角蛋白12的表达水平无明显变化。Agrin还可通过激活角膜缘干细胞的增殖来加速角膜上皮的创伤愈合。在作用机制上，Agrin可促进Yap 1的去磷酸化，从而促进Yap 1的核转位和Cyclin D1的表达，进而促进角膜缘干细胞的增殖。结论Agrin通过Hippo-Yap信号通路促进角膜缘干细胞增殖，加速角膜创伤愈合。
Purpose To investigate the effect and mechanism of Agrin on limbal stem cell proliferation and corneal wound healing. Methods Limbal stem cells were isolated and treated with different concentrations of Agrin. CCK-8 and cell proliferation markers (Ki67 and pH3) were detected to evaluate cell numbers or proliferative potential of limbal stem cells. The corneal epithelium wound model was induced by debridement of central corneal epithelial, and the effects of Agrin on limbal stem cell proliferation and corneal epithelial wound healing rate were determined. Results Agrin promoted the proliferation of cultured limbal stem cells in vitro and increased the expression level of p63α rather than keratin 12. Furthermore, Agrin accelerated the wound healing rate of corneal epithelium through activating limbal stem cell proliferation in vivo. In terms of mechanism, Agrin could facilitate the dephosphorylation of Yap1, which contributed to the nuclear translocation of Yap1 and expression of Cyclin D1, and subsequently promoted proliferation of limbal stem cells. Conclusions Agrin promotes the proliferation of limbal stem cells and accelerates the healing rate of corneal wound through Hippo-Yap signaling pathway.