Integrin-mediated regulation of TGFβ in fibrosis.

Integrin-mediated regulation of TGFβ in fibrosis.
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DOI:
10.1016/j.bbadis.2012.10.005
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发表时间:
2013-07
影响因子:
6.2
通讯作者:
Sheppard, Dean
Sheppard, Dean
中科院分区:
生物学2区
文献类型:
--
作者:
Henderson, Neil C.;Sheppard, Dean

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纤维化是世界范围内发病率和死亡率的主要原因。目前,组织纤维化的治疗选择受到严重限制,器官移植是终末期纤维化疾病的唯一有效治疗方法。然而,对供体器官的需求大大超过供应,因此迫切需要有效的抗纤维化治疗。近年来,细胞粘附受体的整合素家族作为慢性炎症和纤维化的关键调节因子而获得了显著地位。多器官纤维化模型已经证明整合素对纤维化过程具有深远的影响。现在有大量的体内数据表明,在组织纤维化过程中,整合素在不同细胞类型上表达的关键调节作用。在这篇综述中,我们将研究整合素调节这些过程的方式,并讨论如何使用功能阻断抗体和小分子抑制剂操纵整合素可能具有广泛的纤维化疾病患者的治疗中的临床实用性。
Fibrosis is a major cause of morbidity and mortality worldwide. Currently, therapeutic options for tissue fibrosis are severely limited, and organ transplantation is the only effective treatment for end-stage fibrotic disease. However, demand for donor organs greatly outstrips supply, and so effective anti-fibrotic treatments are urgently required. In recent years the integrin family of cell adhesion receptors have gained prominence as key regulators of chronic inflammation and fibrosis. Fibrosis models in multiple organs have demonstrated that integrins have profound effects on the fibrotic process. There is now abundant in vivo data demonstrating critical regulatory roles for integrins expressed on different cell types during tissue fibrogenesis. In this review we will examine the ways in which integrins regulate these processes and discuss how the manipulation of integrins using function blocking antibodies and small molecule inhibitors may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
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