Low density lipoprotein - rosiglitazone - chitosan-calcium alginate/nanoparticles inhibition of human tenon’s fibroblasts activation and proliferation
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Yi Gong2, Jia-Yang Yin1, Bo-Ding Tong1, Jie-Xi Zeng1 and Wei Xiong1
1Department of Ophthalmology and Eye Research Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
2Department of Minimal Invasive Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
Wei Xiong, email: email@example.com
Keywords: low density lipoprotein (LDL), rosiglitazone (RSG), human tenon’s fibroblasts (HTFs), glaucoma filtration surgery (GFS), chitosan-calcium alginate - nanoparticles (CSNP)
Received: April 12, 2017 Accepted: June 30, 2017 Published: October 09, 2017
Anti-fibrotic therapeutic methods with safety and efficiency after glaucoma filtration surgery (GFS) are desirable. In our previous study, by using Human Tenon’s Fibroblasts (HTFs) as a model, we proved the expression of peroxisome proliferator activates receptor-γ (PPAR-γ) in HTFs; in addition, rosiglitazone (RSG), an agonist of PPAR-γ, can inhibit transforming growth factorsβ1 (TGF-β1)-induced reactivation of HTFs, thus to inhibit specifically scarring after GFS through intervening TGF-β/Smads signal pathway. However, a better drug delivery way of RSG, to prolong the duration of its function, and to reduce the toxicity of RSG to ocular tissue still remains challenges. Low density lipoprotein receptor (LDLr) is strongly expressed in hyper-proliferation HTFs after GFS. Therefore, we structured targeting LDL-RSG complexes and channel them into HTFs through LDL-LDLr pathway in order to promote anti-proliferation of HTFs and reduce the toxicity to ocular tissue. Meanwhile, in order to improve the release properties of LDL-RSG complexes, we structured slow release system of LDL-RSG/chitosan-calcium alginate - nanoparticles (CSNP), which effectively inhibited TGF-β1-induced HTFs proliferation, synthesis of extracellular matrix and activation of TGF-β1/SMAD pathway. These data suggested that LDL-RSG/CSNP can be a new anti-fibrotic therapeutic method on scarring after GFS and also a novelty administration of RSG.
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