Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.
Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.
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DOI：
10.1371/journal.pone.0033258
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
García-Bermejo ML
中科院分区：
文献类型：
--
作者：
Conde E;Alegre L;Blanco-Sánchez I;Sáenz-Morales D;Aguado-Fraile E;Ponte B;Ramos E;Sáiz A;Jiménez C;Ordoñez A;López-Cabrera M;del Peso L;de Landázuri MO;Liaño F;Selgas R;Sanchez-Tomero JA;García-Bermejo ML
肾移植术后缺血再灌注（I/R）引起的急性肾小管坏死（ATN）可延迟移植肾功能恢复。鉴定介导保护和/或上皮恢复的因素可能有助于改善移植结果。我们研究了缺氧诱导因子1-α（HIF-1 α）的表达，调节和作用，使用体外和体内实验模型的I/R以及人类移植后肾活检。我们发现，HIF-1 α在缺血期间在近端小管细胞中是稳定的，并且在氧分压正常的晚期再灌注中是出乎意料的。两种诱导都导致体外和体内的基因表达。体外干扰HIF-1 α促进细胞死亡，体内干扰加重组织损伤和肾功能障碍。在移植后的人类活检中，HIF-1 α仅在近端小管中表达，其显示正常的肾结构，与ATN分级呈显著负相关。总之，使用实验模型和人体活检，我们确定了一种新的HIF-1 α诱导在再灌注过程中的肾移植的潜在关键作用。
Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.
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DOI：
10.1097/01.asn.0000074239.22357.06
发表时间：
2003-07-01
影响因子：
13.6
作者：
Matsumoto, M;Makino, Y;Nangaku, M
通讯作者：
Nangaku, M
影响因子：
37.8
作者：
Cai, ZQ;Semenza, GL
通讯作者：
Semenza, GL
影响因子：
2.9
作者：
Natarajan, R;Jones, DG;Fowler, AA
通讯作者：
Fowler, AA
影响因子：
4.8
作者：
Sandau, KB;Zhou, J;Brüne, B
通讯作者：
Brüne, B
DOI：
10.1152/ajprenal.00329.2004
发表时间：
2005-05-01
影响因子：
4.2
作者：
Basile, DP;Fredrich, K;Cowley, AW
通讯作者：
Cowley, AW