Xu Zhuo, Dai Chunsun
Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Kidney Dis (Basel). 2017 Dec;3(4):160-170. doi: 10.1159/000484604. Epub 2017 Nov 16.
Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes. However, the role and mechanisms of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further investigation.
In this study, a mouse model with fibroblast-specific FGFR2 gene disruption was generated. The knockouts were born normal and no kidney dysfunction or histological abnormality was found within 2 months after birth. A kidney ischemia/reperfusion injury (IRI) model was created.
Kidney fibrosis was developed in the control littermates within 2 and 4 weeks after IRI, while in the knockouts, total collagen deposition, fibronectin, and alpha smooth muscle actin expression were decreased compared to those in the control littermates. In addition, the numbers of Ki-67-positive interstitial cells as well as TUNEL-positive interstitial cells were lower in the knockout kidneys at 4 weeks after IRI. Phosphorylated extracellular regulated protein kinase 1/2 was decreased in the knockout kidneys at 2 and 4 weeks after IRI compared to those in the control littermates.
These results suggest that FGF/FGFR2 signaling may promote the proliferation and activation of kidney fibroblasts, which contribute to the development of kidney fibrosis.
成纤维细胞生长因子（FGFs）是参与多种生物学过程的肝素结合蛋白。然而，FGF/FGFR2信号在成纤维细胞活化和肾纤维化中的作用及机制尚需进一步研究。
在本研究中，构建了成纤维细胞特异性FGFR2基因敲除的小鼠模型。基因敲除小鼠出生时正常，出生后2个月内未发现肾功能障碍或组织学异常。建立了肾缺血/再灌注损伤（IRI）模型。
IRI后2周和4周，对照同窝小鼠出现肾纤维化，而与对照同窝小鼠相比，基因敲除小鼠的总胶原沉积、纤连蛋白和α平滑肌肌动蛋白表达降低。此外，IRI后4周，基因敲除小鼠肾脏中Ki-67阳性间质细胞和TUNEL阳性间质细胞数量均减少。与对照同窝小鼠相比，IRI后2周和4周基因敲除小鼠肾脏中磷酸化细胞外调节蛋白激酶1/2水平降低。
这些结果表明，FGF/FGFR2信号可能促进肾成纤维细胞的增殖和活化，从而促进肾纤维化的发展。
