Growth factors and the development of diabetic nephropathy.
Growth factors and the development of diabetic nephropathy.
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DOI：
10.1007/s11892-003-0012-2
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发表时间：
2003-12-01
影响因子：
4.2
通讯作者：
Wolf, Gunter
中科院分区：
文献类型：
--
作者：
Wolf, Gunter
生长因子在与糖尿病肾病相关的功能和结构变化的发展中起重要作用。尽管多年来人们已经知道这些因素对于早期肾肥大和随后的肾小球硬化和肾小管间质纤维化的发展是重要的，但是这些因素中的许多因素的确切分子机制直到最近才被进一步阐明。此外，生长因子还将糖尿病并发症的代谢理论与糖尿病肾病的肾血流动力学改变联系起来，因为某些生长因子可直接影响糖尿病肾病的肾小球血流动力学和肾小管转运。高糖环境刺激细胞摄取葡萄糖和加速非酶反应，导致Amadori修饰的蛋白质和后期发展的晚期糖基化终产物是肾内诱导生长因子的主要刺激物。细胞内反应性物质的产生是这些生长因子的刺激表达中的重要信号中间体。考虑到生长因子在糖尿病肾病发展中的关键作用，拮抗生长因子作用的治疗策略似乎很简单。然而，许多这些因子的多效性功能和它们在正常肾稳态中的生理作用可能使这种方法变得困难。
Growth factors play an important role in the development of functional and structural changes associated with diabetic nephropathy. Although it has been known for years that these factors are important for early renal hypertrophy and subsequent development of glomerulosclerosis and tubulointerstitial fibrosis, the exact molecular mechanism of many of these factors has only recently been more elucidated. Furthermore, growth factors also link the metabolic theory of diabetic complications with renal hemodynamic changes in diabetic nephropathy because some growth factors could directly influence glomerular hemodynamics and tubular transport in diabetic nephropathy. The high glucose environment with stimulated cellular uptake of glucose and accelerated nonenzymatic reactions resulting in Amadori-modified proteins and the later-developing advanced glycation end products are the main stimulators for intrarenal induction of growth factors. Intracellular generation of reactive species is an important signal intermediate in these stimulated expressions of growth factors. Taking into consideration the pivotal role of growth factors in the development of diabetic nephropathy, a therapeutic strategy to antagonize growth factor effects appears to be straightforward. However, the pleiotropic function of many of these factors and their physiologic role in normal renal homeostasis may make this approach difficult.