Keratinocyte growth factor improves repair in the injured tracheal epithelium
Keratinocyte growth factor improves repair in the injured tracheal epithelium
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DOI：
10.1165/rcmb.2006-0384oc
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发表时间：
2007-07-01
影响因子：
6.4
通讯作者：
Strieter, Robert M.
中科院分区：
文献类型：
--
作者：
Gomperts, Brigitte N.;Belperio, John A.;Strieter, Robert M.
角质细胞生长因子（KGF）是肺发育中的关键生长因子，是肺损伤后的保护剂，尽管这种保护作用的确切机制尚未阐明。我们的实验室已经表明，循环上皮祖细胞可以交通到气道，他们似乎是来自骨髓。在此基础上，我们假设KGF及其假定受体（KGFR）对这些细胞很重要。我们发现，KGFR，这是发现几乎只在上皮细胞，是目前在骨髓细胞和循环的小鼠，确定细胞角蛋白5+循环上皮祖细胞（CEPC）的亚群。此外，KGFR与修复近端气道中的细胞角蛋白5+基底细胞群共定位。KGF的全身给药导致细胞角蛋白5+ CEPC在注射后6小时的动员显着增加。给予KGF的小鼠受体的异位同源气管移植导致保护和更快速的修复气管上皮细胞，在气道上皮细胞中的CEPC的数量增加，这种效果被废除阻断CEPC与抗CXCL12抗体。因此，KGF似乎是一个重要的生长因子，为当地居民祖上皮细胞修复和动员和增强植入的CEPC到受损的近端气道上皮。
Keratinocyte growth factor (KGF) is a critical growth factor in lung development and is a protective agent after lung injury, although the exact mechanisms of this protective effect have not yet been elucidated. Our laboratory has shown that circulating epithelial progenitor cells can traffic to the airway and that they appear to be derived from the bone marrow. On this basis, we hypothesized that KGF and its putative receptor (KGFR) would be important to these cells. We showed that the KGFR, which is found almost exclusively on epithelial cells, was present on cells in the bone marrow and circulation of mice that identified a subpopulation of cytokeratin 5+ circulating epithelial progenitor cells (CEPC). In addition, the KGFR co-localized with a population of cytokeratin 5+ basal cells in the repairing proximal airway. Systemic administration of KGF resulted in a significant increase in mobilization of cytokeratin 5+ CEPC at 6 h after injection. Administration of KGF to mouse recipients of heterotopic syngeneic tracheal transplants resulted in protection and more rapid repair of the tracheal epithelium, with an increase in the number of CEPC in the epithelium of the airway, and this effect was abrogated by blocking CEPC with anti-CXCL12 antibodies. KGF therefore appears to be an important growth factor for local resident progenitor epithelial cell repair and for mobilization and enhanced engraftment of CEPC to the injured proximal airway epithelium.