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10.1038/srep43736

http://scihub22266oqcxt.onion/10.1038/srep43736
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suck abstract from ncbi


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pmid28252047
      Sci+Rep 2017 ; 7 (ä): 43736
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  • Inhibition of Proliferation and Epithelial Mesenchymal Transition in Retinal Pigment Epithelial Cells by Heavy Chain-Hyaluronan/Pentraxin 3 #MMPMID28252047
  • He H ; Kuriyan AE ; Su CW ; Mahabole M ; Zhang Y ; Zhu YT ; Flynn HW ; Parel JM ; Tseng SC
  • Sci Rep 2017[Mar]; 7 (ä): 43736 PMID28252047 show ga
  • Proliferative vitreoretinopathy (PVR) is mediated by proliferation and epithelial mesenchymal transition (EMT) of retinal pigment epithelium (RPE). Because heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) purified from human amniotic membrane exerts anti-inflammatory and anti-scarring actions, we hypothesized that HC-HA/PTX3 could inhibit these PVR-related processes in vitro. In this study, we first optimized an ARPE-19 cell culture model to mimic PVR by defining cell density, growth factors, and cultivation time. Using this low cell density culture model and HA as a control, we tested effects of HC-HA/PTX3 on the cell viability (cytotoxicity), proliferation (EGF?+?FGF-2) and EMT (TGF-?1). Furthermore, we determined effects of HC-HA/PTX3 on cell migration (EGF?+?FGF-2?+?TGF-?1) and collagen gel contraction (TGF-?1). We found both HA and HC-HA/PTX3 were not toxic to unstimulated RPE cells. Only HC-HA/PTX3 dose-dependently inhibited proliferation and EMT of stimulated RPE cells by down-regulating Wnt (?-catenin, LEF1) and TGF-? (Smad2/3, collagen type I, ?-SMA) signaling, respectively. Additionally, HA and HC-HA/PTX3 inhibited migration but only HC-HA/PTX3 inhibited collagen gel contraction. These results suggest HC-HA/PTX3 is a non-toxic, potent inhibitor of proliferation and EMT of RPE in vitro, and HC-HA/PTX3's ability to inhibit PVR formation warrants evaluation in an animal model.
  • |Biomarkers [MESH]
  • |C-Reactive Protein/*pharmacology [MESH]
  • |Cell Movement [MESH]
  • |Cell Proliferation/drug effects [MESH]
  • |Cell Survival/drug effects [MESH]
  • |Cells, Cultured [MESH]
  • |Dose-Response Relationship, Drug [MESH]
  • |Epidermal Growth Factor/pharmacology [MESH]
  • |Epithelial Cells/*drug effects/*metabolism/pathology [MESH]
  • |Epithelial-Mesenchymal Transition/*drug effects [MESH]
  • |Humans [MESH]
  • |Hyaluronic Acid/*pharmacology [MESH]
  • |Protein Transport [MESH]
  • |Retinal Pigment Epithelium/*cytology/*metabolism [MESH]
  • |Serum Amyloid P-Component/*pharmacology [MESH]
  • |Signal Transduction/drug effects [MESH]
  • |Smad Proteins/metabolism [MESH]
  • |Transforming Growth Factor beta1/metabolism/pharmacology [MESH]


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