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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.