Tubular Epithelial Cells Transfected With hHGF Counteracts Monocyte Chemotactic Protein-1 Up-regulation After Hypoxia/Reoxygenation Insult
Tubular Epithelial Cells Transfected With hHGF Counteracts Monocyte Chemotactic Protein-1 Up-regulation After Hypoxia/Reoxygenation Insult
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DOI：
10.1016/j.transproceed.2009.05.023
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发表时间：
2009-07-01
影响因子：
0.9
通讯作者：
Grinyo, J. M.
中科院分区：
文献类型：
--
作者：
Franquesa, M.;Riera, M.;Grinyo, J. M.
急性肾损伤（acute kidney injury，阿基）是一种高病死率和高致残率的疾病，主要由肾毒性或缺血性损伤引起。近端肾小管上皮细胞（PTEC）起主要作用。它们是缺血/再灌注损伤的主要靶点。PTEC也被认为是阿基可逆性的效应子，但也是炎症环境的创造者：细胞因子，趋化因子和补体表达。在此过程中涉及的一种重要趋化因子是单核细胞趋化蛋白-1（MCP-1），这是由于其募集和激活单核细胞的能力。肝细胞生长因子（HGF）是一种具有促有丝分裂、抗凋亡和增殖作用的多效性因子，近年来因其抗炎和抗纤维化作用而被研究。我们的目的是评估缺氧和复氧对大鼠PTECs的潜在炎症作用。我们建立了一个稳定的表达人HGF（hHGF）的PTEC细胞系，模拟体内转染，并分析了这种细胞类型在阿基诱导和可逆性中的作用。我们的结果显示用hHGF基因转染促进蛋白质在培养基中持续表达的效率（7627.13 +/- 1144.078至8214.3 +/- 795.37 pg/mL）。当大鼠PTECs处于缺氧/复氧损伤下时，MCP-1高度过表达（4479.3 +/- 154.3 pg/mL蛋白和5.099 +/- 1.23倍对照基因表达）。转染细胞消除了这种效应（288.7 +/- 13.5 pg/mL和1.169 +/- 0.0759倍对照）。总之，我们观察到，缺氧/复氧损伤刺激MCP-1蛋白在PTECs的分泌和稳定转染和过表达hHGF的PTECs废除缺氧/复氧介导的炎症反应，是一个合适的模型，为以后的研究。
Acute kidney injury (AKI) which is mainly produced by nephrotoxic or ischemic insults is correlated with a high mortality and morbidity. Proximal tubular epithelial cells (PTEC) play a major role. They are the main target of ischemia/reperfusion injury. PTECs have also been proposed as the effectors of AKI reversibility, but also as the creator of the inflammatory milieu: cytokine, chemokine, and complement expression. An important chemokine implicated in this process is monocyte chemotactic protein-1 (MCP-1) due to its ability to recruit and activate monocytes. Hepatocyte growth factor (HGF) is a pleiotropic factor with mitogenic, anti-apoptotic, and proliferative effects which has recently been studied for its anti-inflammatory and antifibrogenic effects. Our aim was to evaluate the potential inflammatory effect of hypoxia and reoxygenation on rat PTECs. We created a stable human HGF (hHGF) expressing PTEC line that emulated in vivo transfection and analyzed the role of this cell type in the induction and reversibility of AKI. Our results showed the efficiency of transfection with the hHGF gene to promote sustained expression of the protein in the medium (7627.13 +/- 1144.078 to 8214.3 +/- 795.37 pg/mL). When rat PTECs were under a hypoxia/reoxygenation insult, MCP-1 was highly overexpressed (4479.3 +/- 154.3 pg/mL of protein and 5.099 +/- 1.23 times control gene expression). Transfected cells abrogated this effect (288.7 +/- 13.5 pg/mL and 1.169 +/- 0.0759 times control). In conclusion, we observed that the hypoxia/reoxygenation insult stimulated MCP-1 protein secretion in PTECs and that PTECs which were stably transfected and overexpressing hHGF abrogated the inflammatory reaction mediated by hypoxia/reoxygenation, being a suitable model for later studies.