Norman Jill
UCL Centre for Nephrology, London, UK.
Biochim Biophys Acta. 2011 Oct;1812(10):1327-36. doi: 10.1016/j.bbadis.2011.06.012. Epub 2011 Jul 1.
The age on onset of decline in renal function and end-stage renal disease (ESRD) in autosomal polycystic kidney disease (ADPKD) is highly variable and there are currently no prognostic tools to identify patients who will progress rapidly to ESRD. In ADPKD, expansion of cysts and loss of renal function are associated with progressive fibrosis. Similar to the correlation between tubulointerstitial fibrosis and progression of chronic kidney disease (CKD), in ADPKD, fibrosis has been identified as the most significant manifestation associated with an increased rate of progression to ESRD. Fibrosis in CKD has been studied extensively. In contrast, little is known about the mechanisms underlying progressive scarring in ADPKD although some commonality may be anticipated. Current data suggest that fibrosis associated with ADPKD shares at least some of the "classical" features of fibrosis in CKD (increased interstitial collagens, changes in matrix metalloproteinases (MMPs), over-expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), over-expression of plasminogen activator inhibitor-1 (PAI-1) and increased transforming growth factor beta (TGFβ) but that there are also some unique and stage-specific features. Epithelial changes appear to precede and to drive interstitial changes leading to the proposal that development of fibrosis in ADPKD is biphasic with alterations in cystic epithelia precipitating changes in interstitial fibroblasts and that reciprocal interactions between these cell types drives progressive accumulation of extracellular matrix (ECM). Since fibrosis is a major component of ADPKD it follows that preventing or slowing fibrosis should retard disease progression with obvious therapeutic benefits. The development of effective anti-fibrotic strategies in ADPKD is dependent on understanding the precise mechanisms underlying initiation and progression of fibrosis in ADPKD and the role of the intrinsic genetic defect in these processes. This article is part of a Special Issue entitled: Polycystic Kidney Disease.
常染色体显性多囊肾病（ADPKD）患者出现肾功能下降和终末期肾病（ESRD）的发病年龄差异很大，目前尚无预测工具来识别那些将迅速进展至ESRD的患者。在ADPKD中，囊肿扩大和肾功能丧失与进行性纤维化相关。与肾小管间质纤维化和慢性肾脏病（CKD）进展之间的相关性类似，在ADPKD中，纤维化已被确定为与ESRD进展速率增加相关的最显著表现。CKD中的纤维化已得到广泛研究。相比之下，尽管可能存在一些共性，但对于ADPKD中进行性瘢痕形成的潜在机制知之甚少。目前的数据表明，与ADPKD相关的纤维化至少具有CKD纤维化的一些“经典”特征（间质胶原增加、基质金属蛋白酶（MMPs）变化、金属蛋白酶组织抑制剂-1（TIMP-1）过表达、纤溶酶原激活物抑制剂-1（PAI-1）过表达和转化生长因子β（TGFβ）增加），但也有一些独特的阶段特异性特征。上皮细胞变化似乎先于并驱动间质变化，这导致有人提出ADPKD中纤维化的发展是双相的，囊性上皮细胞的改变促使间质成纤维细胞发生变化，并且这些细胞类型之间的相互作用驱动细胞外基质（ECM）的渐进性积累。由于纤维化是ADPKD的主要组成部分，因此预防或减缓纤维化应能延缓疾病进展，具有明显的治疗益处。ADPKD中有效抗纤维化策略的开发取决于了解ADPKD中纤维化起始和进展的精确机制以及内在基因缺陷在这些过程中的作用。本文是名为：多囊肾病的特刊的一部分。
