Tenascin-C induces transdifferentiation of retinal pigment epithelial cells in proliferative vitreoretinopathy

被引：1

作者：

Zong, Tianyi ^{[1
]}

Mu, Tong ^{[1
]}

Tan, Chengye ^{[1
]}

Xie, Tianhua ^{[1
]}

Zhuang, Miao ^{[1
]}

Wang, Yan ^{[1
]}

Li, Ziwen ^{[1
]}

Yang, Qian ^{[1
,2
]}

Wu, Meili ^{[2
]}

Cai, Jiping ^{[1
]}

Wang, Xiaolu ^{[2
]}

Yao, Yong ^{[1
]}

机构：

[1] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Ophthalmol, Wuxi Med Ctr, 299 Qingyang Rd, Wuxi 214023, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Wuxi Peoples Hosp, Wuxi Med Ctr, Ctr Clin Res, 299 Qingyang Rd, Wuxi 214023, Jiangsu, Peoples R China

来源：

EXPERIMENTAL EYE RESEARCH | 2024年 / 248卷

关键词：

Tenascin-C; Retinal pigment epithelial cells; Transdifferentiation; Proliferative vitreoretinopathy; MESENCHYMAL TRANSITION; TGF-BETA; MODEL;

D O I：

10.1016/j.exer.2024.110097

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

Proliferation and transdifferentiation of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy (PVR); however, the critical regulators of this process remain to be elucidated. Here, we investigated the role of tenascin-C in PVR development. In vitro, exposure of human ARPE-19 (hRPE) cells to TGF-beta 2 increased tenascin-C expression. Tenascin-C was shown to be involved in TGF-beta 2-induced trans- differentiation of hRPE cells, which was inhibited by pretreatment with tenascin-C siRNA. In PVR mouse models, a marked increase in the expression of tenascin-C mRNA and protein was observed. Additionally, immunofluorescence analysis demonstrated a dramatic increase in the colocalization of tenascin-C with RPE65 or alpha-smooth muscle actin(alpha-SMA) in the epiretinal membranes of patients with PVR. There was also abundant expression of integrin alpha V and beta- catenin in the PVR membranes. ICG-001, a beta- catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin alpha V and beta- catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR.

引用

页数：12

共 37 条

[1] Untangling the Extracellular Matrix of Idiopathic Epiretinal Membrane: A Path Winding among Structure, Interactomics and Translational Medicine [J].