Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronic renal disease
Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronic renal disease
复制标题
DOI：
10.1172/jci1709
复制
发表时间：
1998-05-01
影响因子：
15.9
通讯作者：
Nakamura, T
中科院分区：
文献类型：
--
作者：
Mizuno, S;Kurosawa, T;Nakamura, T
慢性肾脏病（CRD）通常被认为是不可治愈的，除非通过肾移植，CRD患者的数量正在增加。肾小球硬化和肾小管间质纤维化代表终末期CRD的形态学等价物。在这项研究中，我们证明了肝细胞生长因子（HGF）对肾功能不全和纤维化的进展的预防作用，使用CRD的自发小鼠模型（ICGN株）。小鼠逐渐发展成肾小球硬化损伤、肾小管萎缩和肾功能不全，直至17周龄。当在4周期间（出生后14-17周）将重组HGF注射到这些小鼠中时，发现肾小管上皮细胞的DNA合成比未注射HGF的小鼠高4.4倍，从而表明HGF促进了肾小管实质扩张。值得注意的是，肝细胞生长因子抑制转化生长因子-β和血小板衍生生长因子的表达，以及在受影响的肾脏肌成纤维细胞的形成。因此，HGF几乎完全抑制肾小管间质纤维化的发生，而HGF减弱肾小球硬化的进展，两者都导致预防肾功能不全的表现。从我们的结果来看，HGF的补充治疗可被考虑作为预防和治疗CRD的新选择。
Chronic renal disease (CRD) is generally thought to be incurable, except through renal transplantation, and the number of patients with CRD is on the increase. Glomerulosclerosis and tubulointerstitial fibrosis represent the morphological equivalent of end-stage CRD. In this study, we demonstrated the preventive effect of hepatocyte growth factor (HGF) on the progression of renal dysfunction and fibrosis, using a spontaneous mouse model for CRD (ICGN strain). The mice progressively developed glomerular sclerotic injury, tubular atrophy, and renal dysfunction until they were 17 wk of age. When recombinant HGF was injected into these mice during a 4-wk-period (from weeks 14-17 after birth), DNA synthesis of tubular epithelial cells was found to be 4.4-fold higher than in mice without HGF injection, thereby suggesting tubular parenchymal expansion promoted by HGF. Notably, HGF suppressed the expression of transforming growth factor-beta and of platelet-derived growth factor as well as myofibroblast formation in the affected kidney. Consequently, the onset of tubulointerstitial fibrosis was almost completely inhibited by HGF, while HGF attenuated the progression of glomerulosclerosis, both leading to preventing manifestation of renal dysfunction, From our results, supplement therapy with HGF may be taken into consideration as a novel option for prevention and treatment of CRD.