Low density lipoprotein - rosiglitazone - chitosan-calcium alginate/nanoparticles inhibition of human tenon's fibroblasts activation and proliferation.

Yi Gong,Bo-Ding Tong,Jie-Xi Zeng,Wei Xiong,Jia-Yang Yin

doi:10.18632/oncotarget.21757

Yi Gong, Bo-Ding Tong + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.21757

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Abstract

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.

Highlights

Epidemiological data show that, after cataract, glaucoma is second main cause leading to loss of vision in the world, and is the world’s second irreversible cause of blindness [1]
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, to inhibit scarring after glaucoma filtration surgery (GFS) through intervening TGF-β/ Smads signal pathway
Results from IF assays showed that α-smooth muscle www.impactjournals.com/oncotarget actin (α-SMA) and Collagen I content was increased by TGF-β1 treatment, whereas reduced by RSG treatment, compared to control group (Figure 1B)

Summary

Introduction

Epidemiological data show that, after cataract, glaucoma is second main cause leading to loss of vision in the world, and is the world’s second irreversible cause of blindness [1]. The essence of the scar formation in the filtering tunnel after glaucoma surgery is the local manifestation of the mechanism of wound healing in the artificial filtering area [3]. During this process, the activation of Human Tenon’s Fibroblasts (HTFs) has been regarded as the main cause of wound repair and scar formation [4, 5]. Transforming growth factors β1 (TGF-β1), an important regulator of wound healing which plays an important role in the formation of scar after GFS, has been regarded as a major inducible factor of HTFs transforming to MFs [8]. TGF-β1-stimulated HTFs were used as cell models to investigate the mechanism and solution strategy of HTFs activation and proliferation

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Conclusion