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肾脏纤维化的机制。

Mechanisms of Renal Fibrosis.

机构信息

Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

出版信息

Annu Rev Physiol. 2018 Feb 10;80:309-326. doi: 10.1146/annurev-physiol-022516-034227. Epub 2017 Oct 25.

Abstract

Tubulointerstitial fibrosis is a chronic and progressive process affecting kidneys during aging and in chronic kidney disease (CKD), regardless of cause. CKD and renal fibrosis affect half of adults above age 70 and 10% of the world's population. Although no targeted therapy yet exists to slow renal fibrosis, a number of important recent advances have clarified the cellular and molecular mechanisms underlying the disease. In this review, I highlight these advances with a focus on cells and pathways that may be amenable to therapeutic targeting. I discuss pathologic changes regulating interstitial myofibroblast activation, including profibrotic and proinflammatory paracrine signals secreted by epithelial cells after either acute or chronic injury. I conclude by highlighting novel therapeutic targets and approaches with particular promise for development of new treatments for patients with fibrotic kidney disease.

摘要

肾小管间质纤维化是一种影响衰老过程中肾脏和慢性肾脏病(CKD)的慢性进行性过程,与病因无关。CKD 和肾纤维化影响了一半以上 70 岁以上的成年人和全球 10%的人口。尽管目前尚无针对肾纤维化的靶向治疗方法,但最近的一些重要进展已经阐明了疾病的细胞和分子机制。在这篇综述中,我重点介绍了这些进展,关注了可能适合治疗靶向的细胞和途径。我讨论了调节间质肌成纤维细胞激活的病理变化,包括上皮细胞在急性或慢性损伤后分泌的促纤维化和促炎旁分泌信号。最后,我强调了一些新的治疗靶点和方法,这些靶点和方法为开发治疗纤维化肾脏疾病的新方法提供了特别有希望的前景。

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