Hewitson Timothy D, Holt Stephen G, Smith Edward R
Department of Nephrology, The Royal Melbourne Hospital, MelbourneVIC, Australia.
Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, MelbourneVIC, Australia.
Front Pharmacol. 2017 Aug 8;8:520. doi: 10.3389/fphar.2017.00520. eCollection 2017.
Although the kidney has capacity to repair after mild injury, ongoing or severe damage results in scarring (fibrosis) and an associated progressive loss of kidney function. However, despite its universal significance, evidence highlights a population based heterogeneity in the trajectory of chronic kidney disease (CKD) in these patients. To explain the heterogeneity of the CKD phenotype requires an understanding of the relevant risk factors for fibrosis. These factors include both the extrinsic nature of injury, and intrinsic factors such as age, gender, genetics, and perpetual activation of fibroblasts through priming. In many cases an additional level of regulation is provided by epigenetic mechanisms which integrate the various pro-fibrotic and anti-fibrotic triggers in fibrogenesis. In this review we therefore examine the various molecular and structural changes of fibrosis, and how they are influenced by extrinsic and intrinsic factors. Our aim is to provide a unifying hypothesis to help explain the transition from acute to CKD.
尽管肾脏在轻度损伤后具有修复能力，但持续或严重的损伤会导致瘢痕形成（纤维化）以及相关的肾功能进行性丧失。然而，尽管其具有普遍意义，但有证据表明这些患者慢性肾脏病（CKD）病程存在基于人群的异质性。要解释CKD表型的异质性，需要了解纤维化的相关风险因素。这些因素包括损伤的外在性质以及内在因素，如年龄、性别、遗传因素，以及通过启动作用使成纤维细胞持续激活。在许多情况下，表观遗传机制提供了额外的调控水平，该机制整合了纤维化形成过程中各种促纤维化和抗纤维化触发因素。因此，在本综述中，我们研究纤维化的各种分子和结构变化，以及它们如何受到外在和内在因素的影响。我们的目的是提供一个统一的假说，以帮助解释从急性肾损伤到CKD的转变。
