title: The effects of pleiotrophin in proliferative vitreoretinopathy.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China.
authors.forename: Enzhong
authors.initials: E
authors.lastname: Jin
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China.
authors.forename: Lvzhen
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Beijing, 100044, China. zhaomingwei64@126.com.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, 100044, China. zhaomingwei64@126.com.|Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, 100044, China. zhaomingwei64@126.com.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D012333:RNA, Messenger; C066845:pleiotrophin
keywords: Epithelial-to-mesenchymal transition (EMT); Pleiotrophin (PTN); Proliferative vitreoretinopathy (PVR); TGF-β; siRNA