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| 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 PVR patients 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 knockdown the expression of PTN. The subsequent effects of PTN inhibition were assessed regarding the EMT, migration, proliferation, cytoskeletal arrangement, TGF-β signaling, PTN signaling, integral tight junction protein expression (e.g., claudin-1 and occludin), 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 evaluated accordingly.
Results: PTN was highly expressed in PVR membranes compared to the 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 the 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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| Keywords:Ophthalmology; Proliferative Vitreoretinopathy (PVR); Pleiotrophin (PTN); Epithelial-to-mesenchymal transition (EMT); TGF-β; siRNA |
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