Can we fight chronic kidney disease by targeting endothelial HB-EGF?
Can we fight chronic kidney disease by targeting endothelial HB-EGF?
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DOI：
10.1152/ajprenal.00345.2016
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
A. Loria
中科院分区：
文献类型：
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作者：
A. Loria
新的证据表明，表皮生长因子受体(EGFR)的过度刺激在高血压相关的慢性肾脏疾病(CKD)的进展中起着关键作用。血管紧张素II在肾脏纤维化病变的发展中起着公认的作用。体外研究表明，肝素结合的表皮生长因子样生长因子(HB-EGFR)配体是慢性血管紧张素II 1型受体(AT1R)刺激下观察到的EGFR反式激活的关键介质。这篇社论重点强调了HB-EGF在体内作用的第一个证据，使用可诱导的cre介导的重组来产生血管内皮细胞中缺乏HB-EGF的小鼠模型。最近发表的这篇论文为HB-EGF在高血压期间血管紧张素Ⅱ/AT1R反式激活EGFR介导的肾组织损伤中的作用提供了强有力的证据。在血管内皮细胞输注的小鼠中，缺乏内皮HB-EGF显示了组织纤维化和损伤的显著减轻，尤其是在但不限于肾脏。
Emerging evidence points to epidermal growth factor receptor (EGFR) overstimulation as a key player in the progression of chronic kidney disease, CKD, associated with hypertension. Angiotensin II has a well-recognized role in the development of renal fibrotic lesions. Compelling in-vitro studies showed that the heparin-binding EGF-like growth factor (HB-EGFR) ligand is a key mediator in the EGFR transactivation observed during chronic angiotensin II type 1 receptor (AT1R) stimulation. This editorial focus highlights the first evidence for the HB-EGF role in vivo using an inducible cre-mediated recombination to generate a mouse model lacking HB-EGF in the vascular endothelial cells. This recent publication provides strong evidence for the role of HB-EGF mediating the AngII/AT1R transactivation of the EGFR-mediated renal tissue damage during hypertension. Absence of endothelial HB-EGF in AngII-infused mice showed a significant attenuation of the tissue fibrosis and damage particularly in, but not limited to, the kidney.