Inhibition of Proliferation and Epithelial Mesenchymal Transition in Retinal Pigment Epithelial Cells by Heavy Chain-Hyaluronan/Pentraxin 3

被引：50

作者：

He, Hua ^{[1
]}

Kuriyan, Ajay E. ^{[2
,3
]}

Su, Chen-Wei ^{[1
]}

Mahabole, Megha ^{[1
]}

Zhang, Yuan ^{[4
,5
]}

Zhu, Ying-Ting ^{[1
]}

Flynn, Harry W. ^{[2
]}

Parel, Jean-Marie ^{[2
]}

Tseng, Scheffer C. G. ^{[1
,4
,5
]}

机构：

[1] TissueTech Inc, Miami, FL 33173 USA

[2] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA

[3] Univ Rochester, Med Ctr, Flaum Eye Inst, Rochester, NY 14642 USA

[4] Ocular Surface Ctr, Miami, FL 33173 USA

[5] Ocular Surface Res & Educ Fdn, Miami, FL 33173 USA

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

COLLAGEN GEL CONTRACTION; RANDOMIZED CONTROLLED-TRIAL; ENDOTHELIAL GROWTH-FACTOR; MOLECULAR-WEIGHT HEPARIN; AMNIOTIC MEMBRANE; RISK-FACTORS; TGF-BETA; IN-VIVO; MYOFIBROBLAST DIFFERENTIATION; CONSTITUTIVE EXPRESSION;

D O I：

10.1038/srep43736

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-beta 1). Furthermore, we determined effects of HC-HA/PTX3 on cell migration (EGF+FGF-2 +TGF-beta 1) and collagen gel contraction (TGF-beta 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 (beta- catenin, LEF1) and TGF-beta (Smad2/3, collagen type I, alpha-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.

引用

页数：15

共 80 条

[1] Vitrectomy with silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy: Results of additional and long-term follow-up - Silicone study report 11 [J].