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首页> 外文期刊>American Journal of Physiology >The effect of high glucose and PPAR-gamma agonists on PPAR-gamma expression and function in HK-2 cells.
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The effect of high glucose and PPAR-gamma agonists on PPAR-gamma expression and function in HK-2 cells.

机译：高葡萄糖和PPAR-γ激动剂对HK-2细胞中PPAR-γ表达和功能的影响。

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摘要

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are ligand-activated transcription factors that regulate cell growth, inflammation, lipid metabolism, and insulin sensitivity. PPAR-gamma in the human kidney has been described. However, the role of PPAR-gamma in proximal tubular cells with respect to cell growth and inflammation in diabetic nephropathy is largely unknown. We evaluated the effect of high (30 mM) D-glucose, thiazolidinedione pioglitazone (10 microM), and the selective PPAR-gamma agonist L-805645 (8 microM) on PPAR-gamma expression, growth, and inflammatory parameters in the proximal tubular model of HK-2 cells. PPAR-gamma was present in HK-2 cells and upregulated with 30 mM D-glucose to 177 +/- 31.2% of control (P < 0.05). PPAR-gamma activation was induced by pioglitazone to a similar level to that observed by exposure to high glucose but maximally induced by the selective agonist L-805645. However, L-805645 reduced cell viability in both 5 and 30 mM d-glucose to 73.8 +/- 3.1and 77.6 +/- 1.4% of control (both P < 0.0001). In parallel, thymidine incorporation was reduced with L-805645 in both 5 and 30 mM D-glucose to 33.3 +/- 3.4 and 37.9 +/- 2.2%, respectively (both P < 0.0001). Flow cytometry demonstrated increased apoptosis and G(1) phase arrest in association with an increase in p21(cip1/waf1) in cells exposed to L-805645. Exposure to 30 mM D-glucose did not significantly change AP-1 promoter activity (89.0 +/- 5.5% of control); however, the addition of L-805645 significantly reduced it to 62.2 +/- 2.7% of control (P < 0.0001). Thirty nanomolar D-glucose induced transforming growth factor-beta(1) to 137.7 +/- 16.9% of control (P < 0.05), and L-805645 was able to suppress this to 68.7 +/- 5.7% of control (P < 0.01 vs. d-glucose). Exposure to 30 mM D-glucose reduced monocyte chemoattractant protein 1 levels to 78.6 +/- 7.1% (P < 0.05) of control, with the reduction more marked in the presence of either pioglitazone (P < 0.01) or L-805645 (P < 0.01). In summary, high glucose upregulates PPAR-gamma and when significantly induced demonstrates anti-proliferative and anti-inflammatory effects.
机译：过氧化物酶体增殖物激活受体-γ（PPAR-γ）是配体激活的转录因子，可调节细胞生长，炎症，脂质代谢和胰岛素敏感性。已经描述了人肾脏中的PPAR-γ。然而，关于糖尿病肾病中的细胞生长和炎症，PPAR-γ在近端肾小管细胞中的作用尚不清楚。我们评估了高（30 mM）D-葡萄糖，噻唑烷二酮吡格列酮（10 microM）和选择性PPAR-γ激动剂L-805645（8 microM）对近端肾小管中PPAR-γ表达，生长和炎症参数的影响HK-2细胞的模型。 PPAR-γ存在于HK-2细胞中，并用30 mM D-葡萄糖上调至对照组的177 +/- 31.2％（P <0.05）。吡格列酮诱导的PPAR-γ激活水平与暴露于高葡萄糖时所观察到的相似，但最大程度由选择性激动剂L-805645诱导。然而，L-805645将5和30 mM d-葡萄糖中的细胞活力均降低至对照的73.8 +/- 3.1和77.6 +/- 1.4％（均P <0.0001）。平行地，在5mM和30mM D-葡萄糖中，用L-805645将胸苷掺入分别降低至33.3 +/- 3.4和37.9 +/- 2.2％（均P ＜0.0001）。流式细胞仪表明增加的细胞凋亡和G（1）阶段逮捕与暴露于L-805645的细胞中p21（cip1 / waf1）的增加有关。暴露于30 mM D-葡萄糖不会显着改变AP-1启动子活性（对照组的89.0 +/- 5.5％）;然而，L-805645的添加将其显着降低至对照的62.2 +/- 2.7％（P <0.0001）。 30纳摩尔D-葡萄糖诱导转化生长因子β（1）达到对照的137.7 +/- 16.9％（P <0.05），L-805645能够将其抑制到对照的68.7 +/- 5.7％（P < 0.01 vs. d-葡萄糖）。暴露于30 mM D-葡萄糖可使单核细胞趋化蛋白1的水平降低至对照的78.6 +/- 7.1％（P <0.05），并且在吡格列酮（P <0.01）或L-805645（P <0.01）。总而言之，高葡萄糖会上调PPAR-γ，当显着诱导时，会表现出抗增殖和抗炎作用。

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