成纤维细胞生长因子1通过抗炎机制改善糖尿病型肾病
文献 Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti-inflammatory mechanism. 发表在 Kidney International 原文链接
Abstract: Inflammation plays a central role in the etiology of diabetic nephropathy, a global health issue. We observed a significant reduction in the renal expression of fibroblast growth factor 1, a known mitogen and insulin sensitizer, in patients with diabetic nephropathy and in mouse models implying that fibroblast growth factor 1 possesses beneficial anti-inflammatory and renoprotective activities in vivo. To test this possibility, we investigated the effects of chronic intraperitoneal administration of fibroblast growth factor 1 into both the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models. Indeed, recombinant fibroblast growth factor 1 significantly suppressed renal inflammation (i.e., cytokines, macrophage infiltration), glomerular and tubular damage, and renal dysfunction in both type 1 and type 2 diabetes mice. Fibroblast growth factor 1 was able to correct the elevated blood glucose levels in type 2 but not in type 1 diabetic mice, suggesting that the anti-inflammatory effect of fibroblast growth factor 1 was independent of its glucose-lowering activity. The mechanistic study demonstrated that fibroblast growth factor 1-mediated inhibition of the renal inflammation in vivo was accompanied by attenuation of the nuclear factor κB and c-Jun N-terminal kinase signaling pathways, further validated in vitro using cultured glomerular mesangial cells and podocytes. Thus, fibroblast growth factor 1 holds great promise for developing new treatments for diabetic nephropathy through countering inflammatory signaling cascades in injured renal tissue.
摘要：糖尿病型肾病作为全球性的健康问题，炎症病因学中起着核心作用。我们观察到糖尿病肾病患者和小鼠模型中成纤维细胞生长因子1（一种已知的促分裂原和胰岛素敏化剂）在肾中表达显着降低，这意味着成纤维细胞生长因子1在体内具有抗炎和肾保护功能。为了测试这种假设，我们
利用链脲霉素诱导的1型糖尿病和db/db 2型糖尿病小鼠模型，通过慢性腹膜内给予成纤维细胞生长因子1，观察其效果。结果显示，重组成纤维细胞生长因子1显着抑制了1型和2型糖尿病小鼠的肾脏炎症（即细胞因子，巨噬细胞浸润），肾小球和肾小管损伤以及肾功能障碍。成纤维细胞生长因子1能够校正2型血糖水平升高，而对1型糖尿病小鼠则无此效果，这表明成纤维细胞生长因子1的抗炎作用与其降低葡萄糖的活性无关。机理研究表明成纤维细胞生长因子1介导的体内肾脏炎症的抑制伴随着核因子κB和c-Jun N端激酶信号传导途径的减弱，进一步在体外使用培养的肾小球系膜细胞和足细胞进行验证。因此，成纤维细胞生长因子1通过在受损肾组织中抵抗炎症信号级联开发新的糖尿病肾病治疗方法具有很大的希望。
使用试剂原文信息：For determination of FGF1 content, the serum was initially diluted 150-fold with 0.01M phosphate-buffered saline (PBS) (pH=7.0-7.2) and was assayed using a human FGF1 enzyme-linked immunosorbent assay kit (Cloud-Clone Corp., Houston, TX) in accordance to the manufacturer’s protocol, and absorbance measured at 450 nm.