期刊
KIDNEY INTERNATIONAL
卷 93, 期 1, 页码 95-109出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2017.05.013
关键词
cytokines; diabetic nephropathy; fibrosis; inflammation; mesangial cells
资金
- Natural Science Foundation of China [81473261, 81622043, 81570744]
- Key Project from Science Technology Department of Zhejiang Province [2016C03G2090419]
- Natural Science Foundation of Zhejiang Province [LQ15H310005, LQ17H070001]
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE013686] Funding Source: NIH RePORTER
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 kappa B 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.
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