Deletion of the Met receptor in the collecting duct decreases renal repair following ureteral obstruction
Deletion of the Met receptor in the collecting duct decreases renal repair following ureteral obstruction
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DOI：
10.1038/ki.2009.304
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发表时间：
2009-10-01
影响因子：
19.6
通讯作者：
Ishibe, Shuta
中科院分区：
文献类型：
--
作者：
Ma, Hong;Saenko, Maryanna;Ishibe, Shuta
肝细胞生长因子及其受体Met激活了肾损伤后修复和再生所必需的生物学途径。Met受体在肾脏内的多种细胞类型中表达，每种细胞类型都能够调节纤维化反应。为了专门研究Met受体在肾损伤期间成人集管中的作用，一种条件敲除小鼠(Met(fl/fl)；生成HoxB7-Cre)，并使用单侧输尿管梗阻（肾元损伤、纤维化和修复模型）进行测试。在这些小鼠中，与输尿管梗阻的非flox窝鼠相比，胶原I和IV以及已知的基质降解调节剂纤溶酶原激活物抑制剂1的表达增加。除肾积水程度与对照组相似外，敲除小鼠间质纤维化、间质浸润和急性肾小管坏死均有增加的趋势。大都会(fl / fl);HoxB7-Cre老鼠;然而，阻塞解除后，小管细胞增殖和肾脏再生能力降低，导致功能恢复减弱。我们认为集束管中的Met受体信号是细胞存活和修复过程的主要调节因子，可能在减少炎症和纤维化反应中起次要作用。国际肾脏杂志（2009）76,868-876；doi: 10.1038 / ki.2009.304;2009年8月12日在线发布
Hepatocyte growth factor and its receptor, Met, activate biological pathways necessary for repair and regeneration following kidney injury. The Met receptor is expressed in multiple cell types within the kidney, each of which is capable of regulating fibrotic responses. To specifically address the role of the Met receptor in the adult collecting duct during renal injury, a conditional knockout mouse (Met(fl/fl);HoxB7-Cre) was generated and tested using unilateral ureteral obstruction, a model of nephron injury, fibrosis, and repair. Following obstruction in these mice there was increased expression of collagens I and IV along with plasminogen activator inhibitor 1, a known regulator of matrix degradation, compared to ureteral obstructed non-flox littermates. There were trends toward increased interstitial fibrosis, infiltration of the interstitium, and acute tubular necrosis in the knockout mice despite similar degrees of hydronephrosis to the control littermates. The Met(fl/fl); HoxB7-Cre mice; however, had reduced tubular cell proliferation and kidney regenerative capacity after release of the obstruction, thus leading to diminished functional recovery. We suggest that Met receptor signaling in the collecting duct acts as a major regulator of cell survival and propagation of the repair process with a possible secondary role to diminish inflammatory and fibrotic responses. Kidney International (2009) 76, 868-876; doi:10.1038/ki.2009.304; published online 12 August 2009