文摘
转化生长因子一个¯¢1-Mediated mRNA表达和氧化应激在肾系膜细胞:比较高的葡萄糖和Hexosamine-Induced基因表达谱
作者(年代):拉蒂P。辛格,戴维斯W。程,燕江,埃罗尔D.Crook最近,我们展示了高葡萄糖和葡萄糖胺硫氧还蛋白相互作用蛋白的诱导表达(TXNIP)和多个基因参与氧化应激和内质的网状压力系膜细胞微阵列研究。转化生长因子(TGF-i¢)1被认为是一个中介的肾脏肥大和ECM基因表达系膜细胞和糖尿病glomerulopathy的发展。这里,我们进一步调查的影响TGF-i¢1 mRNA的表达小鼠系膜细胞行MES-13使用Affymetrix U430 2.0 Oligochips小鼠表达。进一步获得的数据与前面描述的高葡萄糖(HG)和氨基葡萄糖(GlcN)全身的基因表达谱。我们确定了264个基因(我¾总数的0.7% 34000个基因微阵列中)作为TGF-i¢1-regulated基因的161个基因的差异表达是上调1.5倍和85 -基因下调。63 264个基因,也有针对性的和HG的38个基因GlcN虽然13基因通常由三个和其他人是独一无二的TGF-i¢1。生物基于流程的本体论差异表达基因分析表明,多数人参与(i)对生理过程的监管,(ii)新陈代谢,(iii)和DNA结合转录(iv)细胞周期控制和(v)分化。许多基因微阵列实验中标识由量化实际time-PCR进一步验证。TGF-i¢1诱导的表达各种细胞肥厚性和纤维结缔组织生长因子等因素,血小板源生长因子B和成纤维细胞生长因子21。此外,TGF-i¢1增加活性氧(ROS)生成、TXNIP表达和细胞凋亡的系膜细胞TUNEL所揭示。 Extracellular matrix related genes targeted by TGF- ï¢1 are osteopontin, tenascin C, fibronectin, laminin ï¢3, plaminogen activator inhibitor (PAI)-1 and cell surface glycoprotein modifying I-type antigen enzyme, glucosaminyl (N-acetyl) transferase 2. There also exist cross-talks between TGF-ï¢1 and IFN- ï§ signaling pathways as revealed by cis-acting reporter activity assay for STAT3, ï§-activated sequence (GAS) and interferon response sequence element (ISRE). The common targets of HG, GlcN and TGF-ï¢1 induced genes include TXNIP, osteopontin, PAI-1 and others. The results reveal new signaling pathways and gene expression patterns that were not previously understood and reinforces the hypothesis that TGF-ï¢1 mediates several harmful effects of chronic hyperglycemia and hexosamines to generate ROS, ECM accumulation and apoptosis of renal mesangial cells in diabetic glomerulopathy.
