Fine-tuning the ubiquitin-proteasome system to treat pulmonary fibrosis.
Fine-tuning the ubiquitin-proteasome system to treat pulmonary fibrosis.
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DOI：
10.1080/03008207.2018.1529174
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发表时间：
2019-01
影响因子：
2.9
通讯作者：
Romero F
中科院分区：
文献类型：
--
作者：
Roque W;Summer R;Romero F
特发性肺纤维化是一种极具侵袭性的肺部疾病，几乎完全发生在老年人身上，预后非常差，并且缺乏任何真正有效的治疗方法。目前的概念模型是IPF的发展是由于损伤后肺上皮再生能力的年龄相关性下降，主要是由于远端气道中上皮祖细胞的死亡或衰老。这种再生能力的丧失被认为会引发慢性和无效的伤口愈合反应，其特征在于持续的低度肺部炎症和胶原蛋白和其他细胞外基质材料的持续产生。尽管我们对IPF病理生物学的理解最近取得了进展，但仍然迫切需要进一步阐明潜在的机制，以开发更有效的治疗方法。在这篇综述中，我们建立了IPF的许多表现是由于细胞未能有效管理其蛋白质组的情况。我们提出，上皮祖细胞，以及免疫细胞和成纤维细胞成为功能受损，至少在一定程度上，因为积累或损失的各种关键蛋白质的表达。此外，我们提出，这种缺陷的核心是泛素蛋白酶体系统的失调，这是真核细胞中的主要蛋白质降解系统。最后，借用其他领域的概念，我们讨论了如何靶向UPS系统可以作为一种新的治疗IPF和其他纤维化肺病以及。
Idiopathic pulmonary fibrosis is an extremely aggressive lung disease that develops almost exclusively in older individuals, carries a very poor prognosis, and lacks any truly effective therapies. The current conceptual model is that IPF develops because of an age-related decline in the ability of the lung epithelium to regenerate after injury, largely due to death or senescence of epithelial progenitor cells in the distal airways. This loss of regenerative capacity is thought to initiate a chronic and ineffective wound healing response, characterized by persistent, low-grade lung inflammation and sustained production of collagen and other extracellular matrix materials. Despite recent advances in our understanding of IPF pathobiology, there remains a pressing need to further delineate underlying mechanisms to develop more effective therapies for this disease. In this review, we build the case that many of the manifestations of IPF result from a failure of cells to effectively manage their proteome. We propose that epithelial progenitor cells, as well as immune cells and fibroblasts become functionally impaired, at least in part, because of an accumulation or a loss in the expression of various crucial proteins. Further, we propose that central to this defect is the dysregulation of the ubiquitin proteasome system, which is the major protein degradation system in eukaryotic cells. Lastly, borrowing concepts from other fields, we discuss how targeting the UPS system could be employed as a novel treatment for IPF and perhaps for other fibrotic lung diseases as well.
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影响因子：
5.6
作者：
Kendall RT;Feghali-Bostwick CA
通讯作者：
Feghali-Bostwick CA
USP13的下调介导特发性肺纤维化成纤维细胞的表型转化
影响因子：
5.8
作者：
Geng J;Huang X;Li Y;Xu X;Li S;Jiang D;Liang J;Jiang D;Wang C;Dai H
通讯作者：
Dai H
影响因子：
5.8
作者：
Bragoszewski P;Turek M;Chacinska A
通讯作者：
Chacinska A
影响因子：
4.8
作者：
Guzy, Robert D.;Li, Ling;Ornitz, David M.
通讯作者：
Ornitz, David M.
影响因子：
4.4
作者：
Fraser, Emily;Hoyles, Rachel K.
通讯作者：
Hoyles, Rachel K.