Gagliardini Elena, Benigni Ariela
Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24125 Bergamo, Italy.
Cytokine Growth Factor Rev. 2006 Feb-Apr;17(1-2):89-96. doi: 10.1016/j.cytogfr.2005.09.005. Epub 2005 Oct 28.
Chronic kidney diseases are emerging world wide as a public health problem. Finding more effective renoprotective therapies is a major challenge in nephrology. Soon after the discovery of transforming growth factor-beta (TGF-beta), it became clear that this cytokine is widely expressed in almost all kidney cells. Overexpression of TGF-beta isoforms and their receptors in the kidney of experimental animals is closely linked to renal fibrosis, a characteristic feature of progressive proteinuric nephropathies. Antibodies to TGF-beta halt the development of diabetic and non-diabetic nephropathies. The effect is maximized by the addition of TGF-beta antibodies on a background of angiotensin II blockade. Several studies have pointed to a role for TGF-beta in instigating the fibrotic process characteristic of progressive human glomerulopathies, although the possible benefit of selective inhibition of TGF-beta has not been described so far. This chapter discusses the role of TGF-beta in renal fibrosis, and describes the renoprotective potential of strategies that interfere with TGF-beta production in the kidney in experimental animals, as a new anti-fibrotic therapeutic approach.
慢性肾脏病正在全球范围内成为一个公共卫生问题。寻找更有效的肾脏保护疗法是肾脏病学面临的一项重大挑战。在发现转化生长因子-β（TGF-β）后不久，人们就清楚地认识到这种细胞因子在几乎所有肾细胞中广泛表达。实验动物肾脏中TGF-β亚型及其受体的过度表达与肾纤维化密切相关，肾纤维化是进行性蛋白尿性肾病的一个特征。针对TGF-β的抗体可阻止糖尿病和非糖尿病肾病的发展。在血管紧张素II阻断的背景下添加TGF-β抗体可使效果最大化。尽管目前尚未描述选择性抑制TGF-β的潜在益处，但多项研究已指出TGF-β在引发人类进行性肾小球病特征性纤维化过程中所起的作用。本章讨论TGF-β在肾纤维化中的作用，并描述作为一种新的抗纤维化治疗方法，干扰实验动物肾脏中TGF-β产生的策略的肾脏保护潜力。
