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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-05-2017 | Retinal Disorders

The effects of pleiotrophin in proliferative vitreoretinopathy

Authors: Xue Ding, Yujing Bai, Xuemei Zhu, Tianqi Li, Enzhong Jin, Lvzhen Huang, Wenzhen Yu, Mingwei Zhao

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 5/2017

Abstract

Purpose

The purpose of our study was to investigate the effects of pleiotrophin (PTN) in proliferative vitreoretinopathy (PVR) both in vitro and in vivo.

Methods

Immunofluorescence was used to observe the PTN expression in periretinal membrane samples from patients with PVR and controls. ARPE-19 cells were exposed to TGF-β1. The epithelial-to-mesenchymal transition (EMT) of the ARPE-19 cells was confirmed by observed morphological changes and the increased expression of α-SMA and fibronectin at both the mRNA and protein levels. We used specific small interfering (si)RNA to knock down the expression of PTN. The subsequent effects of PTN inhibition were assessed with regard to the EMT, migration, proliferation, cytoskeletal arrangement, TGF-β signaling, PTN signaling, integral tight junction protein expression (e.g., claudin-1 and occludin), and p38 MAPK and p-p38 MAPK levels. Additionally, a PVR rat model was established by the intravitreal injection of ARPE-19 cells transfected with PTN-siRNA and was evaluated accordingly.

Results

PTN was highly expressed in PVR membranes compared to controls. PTN knockdown attenuated the TGF-β1-induced migration, proliferation, cytoskeletal rearrangement, and expression of EMT markers such as α-SMA and fibronectin in the ARPE-19 cells, and these effects may have been mediated through p38 MAPK signaling pathway activation. PTN silencing inhibited the up-regulation of claudin-1 and occludin stimulated by TGF-β1, and PTN knockdown inhibited the proliferative aspects of severe PVR in vivo.

Conclusions

PTN is involved in the process of EMT induced by TGF-β1 in human ARPE-19 cells in vitro, and PTN knockdown attenuated the progression of experimental PVR in vivo. These findings provide new insights into the pathogenesis of PVR.

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Title: The effects of pleiotrophin in proliferative vitreoretinopathy
Authors: Xue Ding
Yujing Bai
Xuemei Zhu
Tianqi Li
Enzhong Jin
Lvzhen Huang
Wenzhen Yu
Mingwei Zhao
Publication date: 01-05-2017
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 5/2017
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-016-3582-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The effects of pleiotrophin in proliferative vitreoretinopathy

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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