低密度脂蛋白-罗格列酮-壳聚糖-海藻酸钙/纳米颗粒对人腱成纤维细胞活化和增殖的抑制作用。,Oncotarget

当前位置： X-MOL 学术 › Oncotarget › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

低密度脂蛋白-罗格列酮-壳聚糖-海藻酸钙/纳米颗粒对人腱成纤维细胞活化和增殖的抑制作用。
Oncotarget Pub Date : 2017-12-30 , DOI: 10.18632/oncotarget.21757
Yi Gong ₁ , Jia-Yang Yin ₂ , Bo-Ding Tong ₂ , Jie-Xi Zeng ₂ , Wei Xiong ₂

Affiliation

在青光眼滤过手术（GFS）之后具有安全性和有效性的抗纤维化治疗方法是理想的。在我们以前的研究中，通过使用人腱纤维细胞（HTF）作为模型，我们证明了过氧化物酶体增殖物的表达激活了HTF中的受体-γ（PPAR-γ）。此外，PPAR-γ的激动剂罗格列酮（RSG）可以抑制转化生长因子β1（TGF-β1）诱导的HTF活化，从而通过干预TGF-β/ Smads信号通路抑制GFS后的特异性瘢痕形成。然而，RSG的更好的药物递送方式，延长其功能的持续时间以及降低RSG对眼组织的毒性仍然是挑战。低密度脂蛋白受体（LDLr）在GFS后的过度增殖HTF中强烈表达。所以，我们构建了针对LDL-RSG复合物的结构，并通过LDL-LDLr途径将其引导进入HTF，以促进HTF的抗增殖并降低对眼组织的毒性。同时，为了改善LDL-RSG复合物的释放性能，我们构建了LDL-RSG /壳聚糖-海藻酸钙-纳米颗粒（CSNP）的缓释体系，有效抑制了TGF-β1诱导的HTFs增殖，细胞外基质合成和TGF-β1/ SMAD途径的激活。这些数据表明，LDL-RSG / CSNP可以作为一种新的抗GFS后瘢痕形成的抗纤维化治疗方法，也是一种新颖的RSG给药方法。我们构建了LDL-RSG /壳聚糖-藻酸钙-纳米颗粒（CSNP）的缓释系统，该系统可有效抑制TGF-β1诱导的HTF增殖，细胞外基质合成和TGF-β1/ SMAD途径的激活。这些数据表明，LDL-RSG / CSNP可以作为一种新的抗GFS后瘢痕形成的抗纤维化治疗方法，也是一种新颖的RSG给药方法。我们构建了LDL-RSG /壳聚糖-藻酸钙-纳米颗粒（CSNP）的缓释系统，该系统可有效抑制TGF-β1诱导的HTF增殖，细胞外基质合成和TGF-β1/ SMAD途径的激活。这些数据表明，LDL-RSG / CSNP可以作为一种新的抗GFS后瘢痕形成的抗纤维化治疗方法，也是一种新颖的RSG给药方法。

"点击查看英文标题和摘要"

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

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.

更新日期：2019-11-01

点击分享查看原文

点击收藏

公开下载