Sustained release of hepatocyte growth factor by cationic self-assembling peptide/heparin hybrid hydrogel improves β-cell survival and function through modulating inflammatory response.
Sustained release of hepatocyte growth factor by cationic self-assembling peptide/heparin hybrid hydrogel improves β-cell survival and function through modulating inflammatory response.
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DOI：
10.2147/ijn.s108921
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发表时间：
2016
影响因子：
8
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Liu S;Zhang L;Cheng J;Lu Y;Liu J
炎症反应是胰岛移植中移植物功能障碍的主要原因。肝细胞生长因子（HGF）在多种疾病中显示出抗炎活性。本研究旨在通过自组装肽/肝素（SAP/Hep）杂化凝胶递送HGF，以保护β细胞免受炎症损伤。分析了SAP的形态和缓释性能。采用体外培养的大鼠INS-1 β细胞系，经肿瘤坏死因子α（TNF α）处理后，移植于大鼠肾包膜内，观察移植后β细胞的活性、凋亡、功能及炎症反应。阳离子KLD 1 R和KLD 2 R自组装形成的水凝胶由于静电作用对Hep和HGF具有更高的结合亲和力。HGF从阳离子SAP/Hep凝胶中的缓慢释放是一个涉及与Hep的结合亲和力和分子扩散的两步机制。体内外实验结果表明，载HGF的KLD 2 R/Hep凝胶可促进胰岛β细胞存活和胰岛素分泌，抑制胰岛β细胞凋亡、细胞因子释放、T细胞浸润和NFκB/p38 MAPK通路的激活。本研究提示SAP/Hep凝胶是一种很有前途的胰岛移植生物活性蛋白局部递送载体。
Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated. Cationic KLD1R and KLD2R self-assembled to nanofiber hydrogel, which showed higher binding affinity for Hep and HGF because of electrostatic interaction. Slow release of HGF from cationic SAP/Hep gel is a two-step mechanism involving binding affinity with Hep and molecular diffusion. In vitro and in vivo results showed that HGF-loaded KLD2R/Hep gel promoted β-cell survival and insulin secretion, and inhibited cell apoptosis, cytokine release, T-cell infiltration, and activation of NFκB/p38 MAPK pathways in β-cells. This study suggested that SAP/Hep gel is a promising carrier for local delivery of bioactive proteins in islet transplantation.