Troglitazone suppresses the secretion of type I collagen by mesangial cells in vitro
Troglitazone suppresses the secretion of type I collagen by mesangial cells in vitro
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DOI：
10.1046/j.1523-1755.2002.00277.x
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发表时间：
2002-04-01
影响因子：
19.6
通讯作者：
McCarthy, KJ
中科院分区：
文献类型：
--
作者：
Routh, RE;Johnson, JH;McCarthy, KJ
背景。我们的实验室已证明曲格列酮（一种噻唑烷二酮和过氧化物酶体增殖物激活受体γ (PPAR-γ) 激动剂）可预防糖尿病大鼠的系膜扩张和肾小球硬化。我们研究并比较了两种 PPAR 激动剂在系膜细胞水平的作用。方法。大鼠系膜细胞在含有 5 mmol/L 葡萄糖、30 mmol/L 葡萄糖或 5 mmol/L 葡萄糖加 25 mmol/L 甘露醇的培养基中生长。培养物要么不处理，要么用 10 mumol/L 曲格列酮 (PPAR-gamma) 或 100 mumol/L 氯贝丁酯 (PPAR-alpha) 处理。使用以下参数评估系膜细胞反应：PPAR-γ和-α mRNA的检测、PPAR-γ和-α激活程度、扩散细胞面积、总蛋白产生以及层粘连蛋白和I型胶原产生。结果。逆转录聚合酶链反应 (RT-PCR) 显示大鼠系膜细胞中存在 PPAR-γ 和 -α mRNA。 PPAR-γ 和-α 蛋白在系膜细胞中具有活性，并且激活程度受不同血糖条件的影响。曲格列酮和氯贝特治疗部分纠正了高血糖条件下系膜细胞扩散细胞面积的增加。然而，这两种激动剂都不能纠正高血糖引起的总蛋白产量的增加。在两种培养基条件下，曲格列酮治疗导致 I 型胶原显着、特异性减少，同时层粘连蛋白产量略有减少。氯贝丁酯在任一培养基条件下对层粘连蛋白合成均无影响，但会降低高血糖条件下生长的细胞中 I 型胶原蛋白的合成。结论。 PPAR-α 和 -γ mRNA 信号通路在系膜细胞中就位且活跃。两种激动剂都会影响系膜细胞的表型行为并改善高血糖引起的变化。数据表明，曲格列酮对系膜细胞表型的校正可能影响这些细胞的病理性纤维化结缔组织基质（即，I型胶原）的产生/沉积。
Background. Our laboratory has shown that troglitazone, a thiazolidinedione and peroxisomal proliferator activated receptor gamma (PPAR-gamma) agonist, prevents mesangial expansion and Glomerulosclerosis in diabetic rats. We investigated and compared the action of two PPAR agonists at the level of the mesangial cell.Methods. Rat mesangial cells were grown in medium containing 5 mmol/L glucose, 30 mmol/L glucose, or 5 mmol/L glucose plus 25 mmol/L mannitol. The cultures were either left untreated, treated with 10 mumol/L troglitazone (PPAR-gamma), or 100 mumol/L clofibrate (PPAR-alpha). The following parameters were used to assess mesangial cell responses: detection of PPAR-gamma and -alpha mRNA, the degree of PPAR-gamma and -alpha activation, spread cell area, total protein production, and laminin and type I collagen production.Results. Reverse transcription-polymerase chain reaction (RT-PCR) showed the presence of PPAR-gamma and -alpha mRNA in rat mesangial cells. PPAR-gamma and -alpha proteins are active in mesangial cells and the extent of activation is affected by different glycemic conditions. Troglitazone and clofibrate treatment corrected in part the increase in spread cell area seen in mesangial cells in hyperglycemic conditions. However, neither agonist corrected the increase in total protein production induced by hyperglycemia. Treatment with troglitazone resulted in a significant, specific decrease in type I collagen along with a slight decrease in laminin production in both medium conditions. Clofibrate had no effect on laminin synthesis in either medium condition but did decrease type I collagen synthesis in cells grown in hyperglycemic conditions.Conclusion. PPAR-alpha and -gamma mRNA signaling, pathways are in place and active in mesangial cells. Both agonists affect the phenotypic behavior of mesangial cells and ameliorate changes resulting from hyperglycemia. The data indicate that the correction of mesangial cell phenotype by troglitazone may influence production/deposition of a pathological fibrotic connective tissue matrix (that is, type I collagen) by these cells.