Connective tissue growth factor promotes retinal pigment epithelium mesenchymal transition via the PI3K/AKT signaling pathway

Wang,Yafen; Chang,Tianfang; Wu,Tong; Ye,Wei; Wang,Yusheng; Dou,Guorui; Du,Hongjun; Hui,Yannian; Guo,Changmei

doi:10.3892/mmr.2021.12028

Connective tissue growth factor promotes retinal pigment epithelium mesenchymal transition via the PI3K/AKT signaling pathway

Authors:
- Yafen Wang
- Tianfang Chang
- Tong Wu
- Wei Ye
- Yusheng Wang
- Guorui Dou
- Hongjun Du
- Yannian Hui
- Changmei Guo
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Affiliations: Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: March 22, 2021 https://doi.org/10.3892/mmr.2021.12028
Article Number: 389
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Proliferative vitreoretinopathy (PVR) is a disease leading to the formation of contractile preretinal membranes (PRMs) and is one of the leading causes of blindness. Connective tissue growth factor (CTGF) has been identified as a possible key determinant of progressive tissue fibrosis and excessive scarring. Therefore, the present study investigated the role and mechanism of action of CTGF in PVR. Immunohistochemical staining was performed to detect the expression of CTGF, fibronectin and collagen type III in PRMs from patients with PVR. The effects and mechanisms of recombinant human CTGF and its upstream regulator, TGF‑β1, on epithelial‑mesenchymal transition (EMT) and the synthesis of extracellular matrix (ECM) by retinal pigment epithelium (RPE) cells were investigated using reverse transcription‑quantitative PCR, western blotting and a [³H]proline incorporation assay. The data indicated that CTGF, fibronectin and collagen type III were highly expressed in PRMs. In vitro, CTGF significantly decreased the expression of the epithelial markers ZO‑1 and E‑cadherin and increased that of the mesenchymal markers fibronectin, N‑cadherin and α‑smooth muscle actin in a concentration‑dependent manner. Furthermore, the expression of the ECM protein collagen type III was upregulated by CTGF. However, the trends in expression for the above‑mentioned markers were reversed after knocking down CTGF. The incorporation of [³H]proline into RPE cells was also increased by CTGF. In addition, 8‑Bromoadenosine cAMP inhibited CTGF‑stimulated collagen synthesis and transient transfection of RPE cells with a CTGF antisense oligonucleotide inhibited TGF‑β1‑induced collagen synthesis. The phosphorylation of PI3K and AKT in RPE cells was promoted by CTGF and TGF‑β1 and the latter promoted the expression of CTGF. The results of the present study indicated that CTGF may promote EMT and ECM synthesis in PVR via the PI3K/AKT signaling pathway and suggested that targeting CTGF signaling may have a therapeutic or preventative effect on PVR.

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