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The effects of pleiotrophin in proliferative vitreoretinopathy

  • Retinal Disorders
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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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Acknowledgements

We would like to thank Youzhi Yu for her help with the immunofluorescence assays and Yang Li for suggesting the Western blot analysis.

Author contributions

Research design: D. Xue, Y.J. Bai

Experiments: D. Xue

Data analysis: D. Xue, Y.J. Bai

Manuscript writing: D. Xue, Y.J. Bai

Manuscript review: Y.J. Bai, M.W. Zhao

Grant acquisition: M.W. Zhao

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    Authors and Affiliations

    1. Department of Ophthalmology, Peking University People’s Hospital, Beijing, 100044, China

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

    2. Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China

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

    3. Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China

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

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    Correspondence to Mingwei Zhao.

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    Funding

    This work was supported by the National Natural Science Foundation of China (grant nos. 81470651 and 81570858) and the Specialized Research Fund for the Doctoral Program of Higher Education for ZMW (20130001110086). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

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    All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Xue Ding and Yujing Bai contributed equally to this work.

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    Ding, X., Bai, Y., Zhu, X. et al. The effects of pleiotrophin in proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 255, 873–884 (2017). https://doi.org/10.1007/s00417-016-3582-9

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