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肾移植中的纤维化发生机制:预防和治疗的潜在靶点。

Fibrogenesis in kidney transplantation: potential targets for prevention and therapy.

机构信息

Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53793, USA.

出版信息

Transplantation. 2009 Nov 27;88(10):1149-56. doi: 10.1097/TP.0b013e3181bcccea.

DOI:10.1097/TP.0b013e3181bcccea
PMID:19935366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2784657/
Abstract

Kidney allograft fibrosis results from a reactive process mediated by humoral and cellular events and the activation of transforming growth factor beta1. It is a process that involves both parenchymal and graft infiltrating cells and can lead to organ failure if injury persists or if the response to injury is excessive. In this review, we will address the role of preventive and therapeutic strategies that target kidney allograft fibrogenesis. We conclude that in addition to preventive strategies, therapies based on bone morphogenetic protein 7, hepatocyte growth factor, connective tissue growth factor, and pirfenidone have shown promising results in preclinical studies. Clinical trials are needed to examine the effect of these therapies on long-term outcomes.

摘要

肾移植纤维化是由体液和细胞事件介导的反应过程以及转化生长因子 β1 的激活引起的。这是一个涉及实质细胞和移植物浸润细胞的过程,如果损伤持续存在或对损伤的反应过度,可能导致器官衰竭。在这篇综述中,我们将讨论针对肾移植纤维化的预防和治疗策略的作用。我们的结论是,除了预防策略外,基于骨形态发生蛋白 7、肝细胞生长因子、结缔组织生长因子和吡非尼酮的治疗在临床前研究中显示出了有希望的结果。需要进行临床试验来研究这些治疗方法对长期结果的影响。

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1
Fibrogenesis in kidney transplantation: potential targets for prevention and therapy.肾移植中的纤维化发生机制:预防和治疗的潜在靶点。
Transplantation. 2009 Nov 27;88(10):1149-56. doi: 10.1097/TP.0b013e3181bcccea.
2
Therapeutic targets in the treatment of allograft fibrosis.同种异体移植纤维化治疗中的治疗靶点。
Am J Transplant. 2006 May;6(5 Pt 1):867-75. doi: 10.1111/j.1600-6143.2006.01261.x.
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Beneficial effects of CCR1 blockade on the progression of chronic renal allograft damage.CCR1阻断对慢性肾移植损伤进展的有益作用。
Am J Transplant. 2007 Mar;7(3):527-37. doi: 10.1111/j.1600-6143.2006.01654.x. Epub 2007 Jan 4.
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Chemokines in transplant rejection.移植排斥反应中的趋化因子
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Chemokine-directed strategies to attenuate allograft rejection.趋化因子导向的减轻同种异体移植排斥反应的策略。
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T-cell growth factors in allograft rejection and tolerance.同种异体移植排斥反应和耐受中的T细胞生长因子。
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BMP7 regulates lung fibroblast proliferation in newborn rats with bronchopulmonary dysplasia.BMP7 调控支气管肺发育不良新生大鼠肺成纤维细胞增殖。
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本文引用的文献

1
EMT: when epithelial cells decide to become mesenchymal-like cells.上皮-间质转化:上皮细胞决定转变为间充质样细胞的过程。
J Clin Invest. 2009 Jun;119(6):1417-9. doi: 10.1172/JCI39675.
2
Fibroblast activation and myofibroblast generation in obstructive nephropathy.梗阻性肾病中的成纤维细胞活化与肌成纤维细胞生成
Nat Rev Nephrol. 2009 Jun;5(6):319-28. doi: 10.1038/nrneph.2009.74.
3
Nox-2 is a modulator of fibrogenesis in kidney allografts.Nox-2是同种异体肾移植中纤维生成的调节因子。
Am J Transplant. 2009 Jan;9(1):74-82. doi: 10.1111/j.1600-6143.2008.02463.x. Epub 2008 Oct 31.
4
Inhibition of connective tissue growth factor by small interfering RNA prevents renal fibrosis in rats undergoing chronic allograft nephropathy.小干扰RNA抑制结缔组织生长因子可预防慢性移植肾肾病大鼠的肾纤维化。
Transplant Proc. 2008 Sep;40(7):2365-9. doi: 10.1016/j.transproceed.2008.07.100.
5
CTGF inhibits BMP-7 signaling in diabetic nephropathy.结缔组织生长因子在糖尿病肾病中抑制骨形态发生蛋白-7信号通路。
J Am Soc Nephrol. 2008 Nov;19(11):2098-107. doi: 10.1681/ASN.2007111261. Epub 2008 Jul 16.
6
Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial fibrosis.上皮-间质转化与慢性移植肾肾小管间质纤维化
Transplant Rev (Orlando). 2008 Jan;22(1):1-5. doi: 10.1016/j.trre.2007.09.004.
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Anti-VEGF therapy: the search for clinical biomarkers.抗血管内皮生长因子治疗:寻找临床生物标志物。
Expert Rev Mol Diagn. 2008 May;8(3):301-14. doi: 10.1586/14737159.8.3.301.
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Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia.一项双盲、安慰剂对照研究的结果,该研究旨在评估肌肉注射肝细胞生长因子质粒改善严重肢体缺血患者肢体灌注的安全性。
Circulation. 2008 Jul 1;118(1):58-65. doi: 10.1161/CIRCULATIONAHA.107.727347. Epub 2008 Jun 16.
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HGF as a renotrophic and anti-fibrotic regulator in chronic renal disease.肝细胞生长因子作为慢性肾病中的一种肾营养和抗纤维化调节剂。
Front Biosci. 2008 May 1;13:7072-86. doi: 10.2741/3211.
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Bone morphogenetic protein-7 (BMP7) in chronic kidney disease.慢性肾脏病中的骨形态发生蛋白-7(BMP7)
Front Biosci. 2008 May 1;13:4726-39. doi: 10.2741/3035.