Open AccessInhibition of Proliferation and Epithelial Mesenchymal Transition in Retinal Pigment Epithelial Cells by Heavy Chain-Hyaluronan/Pentraxin 3
Author(s) -
Hua He,
Ajay E. Kuriyan,
Chen Wei Su,
Megha Mahabole,
Yuan Zhang,
Yingting Zhu,
Harry W. Flynn,
Jean Marie Parel,
Scheffer C.G. Tseng
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep43736
Subject(s) - ptx3 , epithelial–mesenchymal transition , cell growth , proliferative vitreoretinopathy , chemistry , microbiology and biotechnology , cell migration , wnt signaling pathway , cell culture , fibroblast , hyaluronic acid , cell , mesenchymal stem cell , in vitro , signal transduction , biology , biochemistry , retinal , downregulation and upregulation , immunology , inflammation , anatomy , retinal detachment , genetics , gene
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-β1). Furthermore, we determined effects of HC-HA/PTX3 on cell migration (EGF + FGF-2 + TGF-β1) and collagen gel contraction (TGF-β1). 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 (β-catenin, LEF1) and TGF-β (Smad2/3, collagen type I, α-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.