Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD).
Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD).
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DOI：
10.1016/j.bbadis.2011.06.012
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发表时间：
2011-10
影响因子：
6.2
通讯作者：
Norman, Jill
中科院分区：
文献类型：
--
作者：
Norman, Jill
关键词：
常染色体多囊肾病 (ADPKD) 中肾功能下降和终末期肾病 (ESRD) 的发病年龄差异很大，目前尚无预后工具来识别将迅速进展为 ESRD 的患者。在 ADPKD 中，囊肿扩张和肾功能丧失与进行性纤维化有关。与肾小管间质纤维化和 CKD 进展之间的相关性类似，在 ADPKD 中，纤维化已被确定为与 ESRD 进展率增加相关的最显着表现。 CKD 中的纤维化已得到广泛研究。相比之下，尽管可以预期存在一些共性，但人们对 ADPKD 进行性疤痕形成的机制知之甚少。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、MMP 变化、TIMP-1 过度表达、PAI-1 过度表达和 TGFβ 增加），但也存在一些独特的阶段特异性特征。上皮变化似乎先于并驱动间质变化，从而提出 ADPKD 中纤维化的发展是双相的，囊性上皮的变化引发间质成纤维细胞的变化，并且这些细胞类型之间的相互作用驱动了 ECM 的逐渐积累。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，并具有明显的治疗益处。 ADPKD 有效抗纤维化策略的开发取决于对 ADPKD 纤维化起始和进展的精确机制以及内在遗传缺陷在这些过程中的作用的了解。
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 is associated with progressive fibrosis. Similar to the correlation between tubulointerstitial fibrosis and progression of 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 MMPs, over-expression of TIMP-1, over-expression of PAI-1 and increased 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 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.
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影响因子：
2.9
作者：
Gallagher AR;Germino GG;Somlo S
通讯作者：
Somlo S
DOI：
10.1073/pnas.211191098
发表时间：
2001-10-09
影响因子：
11.1
作者：
Boulter, C;Mulroy, S;Sandford, R
通讯作者：
Sandford, R
影响因子：
19.6
作者：
Bello-Reuss, E;Holubec, K;Rajarman, S
通讯作者：
Rajarman, S
DOI：
10.1083/jcb.201006173
发表时间：
2010-11-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chapin HC;Caplan MJ
通讯作者：
Caplan MJ
影响因子：
13.6
作者：
Chung, Arthur C. K.;Huang, Xiao R.;Lan, Hui Y.
通讯作者：
Lan, Hui Y.