Novel cystogenic role of basic fibroblast growth factor in developing rodent kidneys
Novel cystogenic role of basic fibroblast growth factor in developing rodent kidneys
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DOI：
10.1152/ajprenal.00382.2005
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Ray, Patricio E.
中科院分区：
文献类型：
--
作者：
Li, Zhuangwu;Jerebtsova, Marina;Ray, Patricio E.
碱性成纤维细胞生长因子（bFGF）是一种肝素结合生长因子，在人类发育不良和囊性肾脏疾病中积累。既往研究表明bFGF可以调节发育中的肾小管的生长；然而，其在肾囊肿形成的发病机制中的作用尚不清楚。在这里，我们验证了在发育中的啮齿动物肾脏中bFGF过表达诱导体内囊肿形成的假设。我们使用两种不同的腺病毒介导的基因转移方法在发育中的啮齿动物肾脏中过表达bFGF。首先，用编码人bFGF或LacZ基因的腺病毒载体（rAd）感染胚胎期第15天的Sprague-Dawley大鼠后肾（MK）外植体，移植到成年雌性大鼠的肾包膜下。随后，为了确定bFGF是否能在肾收集系统完整的发育肾脏中诱导肾囊肿，我们在新生小鼠眶后神经丛中注射rAd-bFGF或LacZ载体。基础FGF诱导MK外植体更有效地融入宿主肾脏，并增加发育中的小管的血管化和增殖，导致小管扩张和肾囊肿的快速形成。此外，我们成功地在新生小鼠肾脏中表达了人bFGF，并诱导肾小管扩张和肾囊肿。相反，注射rAd-lacZ的小鼠没有出现肾小管扩张或肾囊肿。据我们所知，这些实验首次表明bFGF在发育中的啮齿动物肾脏中过表达可以诱导体内肾囊肿的形成。
Basic fibroblast growth factor (bFGF) is a heparin-binding growth factor that is accumulated in human dysplastic and cystic renal diseases. Previous studies have shown that bFGF can modulate the growth of developing renal tubules; however, its role in the pathogenesis of renal cyst formation is not clearly understood. Here, we tested the hypothesis that overexpression of bFGF in developing rodent kidneys induces cyst formation in vivo. We used two different adenoviral-mediated gene-transferring approaches to overexpress bFGF in developing rodent kidneys. Initially, metanephric kidney (MK) explants harvested from embryonic day 15 Sprague-Dawley rats were infected with adenoviral vectors (rAd) encoding human bFGF or LacZ genes and transplanted under the renal capsule of adult female rats. Subsequently, to determine whether bFGF could induce renal cysts in developing kidneys with an intact renal collecting system, we injected rAd-bFGF or LacZ vectors in the retroorbital plexus of newborn mice. Basic FGF induced a more efficient integration of the MK explants into the host kidneys and increased the vascularization and proliferation of developing tubules, leading to tubular dilatation and rapid formation of renal cysts. In addition, we successfully expressed human bFGF in the kidney of newborn mice in vivo and induced tubular dilatation and renal cysts. In contrast, mice injected with rAd-lacZ did not develop tubular dilatation or renal cysts. To the best of our knowledge, these experiments show for the first time that overexpression of bFGF in developing rodent kidneys can induce the formation of renal cysts in vivo.