p70S6K激活促进翼状胬肉组织在角膜上生长时成纤维细胞向肌成纤维细胞的转分化。

p70S6K activation promotes the transdifferentiation of fibroblasts to myofibroblasts in pterygium tissue growth on the cornea.

作者信息

Zhao Xin-Rong, Zhang Ming-Chang, Xie Hua-Tao, Ji Nan, Sun Le-Tian

机构信息

Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.

Department of Ophthalmology, The First Affiliated Hospital of Medical College, Shihezi University, Shihezi, Xin Jiang, China.

出版信息

Biotechnol Lett. 2018 Feb;40(2):437-444. doi: 10.1007/s10529-017-2488-x. Epub 2017 Dec 21.

DOI:10.1007/s10529-017-2488-x

PMID:29270715

Abstract

OBJECTIVE

To investigate the role of p70S6K in the transdifferentiation of fibroblasts to myofibroblasts in pterygium tissue growth on the cornea.

RESULTS

Quantitative real-time PCR and immunohistochemistry showed that p70S6K expression was higher in pterygium tissues than in normal conjunctival tissues. Higher p70S6K RNA expression levels were correlated with higher pterygium grades. Additionally, western blot analysis revealed that phosphorylated (activated) p70S6K (p-p70S6K) expression was significantly correlated with α-smooth muscle actin (α-SMA, a hallmark of transdifferentiation) expression in cultured human pterygium fibroblasts (HPFs). Furthermore, p70S6K knockdown and the specific mTOR inhibitor rapamycin decreased the expression levels of p-p70S6K and α-SMA in cultured fibroblasts from grade T3 pterygium.

CONCLUSIONS

p70S6K activation promotes the transdifferentiation of pterygium fibroblasts to myofibroblasts. Thus, targeting p70S6K may be a useful strategy in the management of pterygium.

摘要

目的

探讨p70S6K在翼状胬肉组织于角膜生长过程中成纤维细胞向肌成纤维细胞转分化中的作用。

结果

定量实时聚合酶链反应和免疫组织化学显示，翼状胬肉组织中p70S6K表达高于正常结膜组织。较高的p70S6K RNA表达水平与较高的翼状胬肉分级相关。此外，蛋白质印迹分析显示，在培养的人翼状胬肉成纤维细胞（HPF）中，磷酸化（活化）的p70S6K（p-p70S6K）表达与α平滑肌肌动蛋白（α-SMA，转分化的标志）表达显著相关。此外，p70S6K基因敲低和特异性mTOR抑制剂雷帕霉素降低了T3级翼状胬肉培养成纤维细胞中p-p70S6K和α-SMA的表达水平。