Low density lipoprotein - rosiglitazone - chitosan-calcium alginate/nanoparticles inhibition of human tenon's fibroblasts activation and proliferation.
Low density lipoprotein - rosiglitazone - chitosan-calcium alginate/nanoparticles inhibition of human tenon's fibroblasts activation and proliferation.
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DOI：
10.18632/oncotarget.21757
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发表时间：
2017-12-01
期刊：
影响因子：
--
通讯作者：
Xiong W
中科院分区：
文献类型：
--
作者：
Gong Y;Yin JY;Tong BD;Zeng JX;Xiong W
青光眼滤过手术（GFS）后安全有效的抗纤维化治疗方法是理想的。本课题组前期以人眼球筋膜成纤维细胞（Human Tenon’s Fibroblasts，HTFs）为模型，证实HTFs中存在过氧化物酶体增殖物激活受体-γ（peroxisome proliferator activates receptor-γ，PPAR-γ）的表达，同时发现PPAR-γ激动剂罗格列酮（rosiglitazone，RSG）可抑制转化生长因子β1（transforming growth factors β 1，TGF-β1）诱导的HTFs再激活，从而通过干预TGF-β/Smads信号通路特异性抑制GFS后瘢痕形成。然而，寻找更好的给药途径，延长其作用的持续时间，降低其对眼组织的毒性仍是一个挑战。低密度脂蛋白受体（LDLr）在GFS后的过度增殖HTFs中强烈表达。因此，我们构建了靶向LDL-RSG复合物，并通过LDL-LDLr通路将其导入HTFs，以促进HTFs的抗增殖作用，降低对眼组织的毒性。同时，为了改善LDL-RSG复合物的释药性能，我们构建了LDL-RSG/壳聚糖-海藻酸钙-纳米粒（CSNP）缓释体系，该体系能有效抑制TGF-β1诱导的HTFs增殖、细胞外基质合成及TGF-β1/SMAD通路的激活。提示LDL-RSG/CSNP可作为一种新的抗纤维化治疗方法，也是RSG的一种新奇的给药途径。
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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