Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti-inflammatory mechanism.

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.

• Authors: Guang Liang, Lintao Song, Zilu Chen, Yuanyuan Qian, Junjun Xie, Longwei Zhao, Qian Lin, Guanghui Zhu, Yi Tan, Xiaokun Li, Moosa Mohammadi, Zhifeng Huang
• Journal: Kidney international (Kidney Int) Vol. 93 Issue 1 Pg. 95-109 (01 2018) ISSN: 1523-1755 [Electronic] United States
• PMID: 28750927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Blood Glucose
• Cytokines
• Inflammation Mediators
• NF-kappa B
• Recombinant Proteins
• Fibroblast Growth Factor 1
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Blood Glucose (drug effects, metabolism)
• Cell Line
• Cytokines (metabolism)
• Diabetes Mellitus, Experimental (blood, complications, drug therapy)
• Diabetes Mellitus, Type 1 (blood, complications, drug therapy)
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy)
• Diabetic Nephropathies (blood, etiology, pathology, prevention & control)
• Fibroblast Growth Factor 1 (blood, pharmacology)
• Humans
• Inflammation Mediators (metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Kidney (drug effects, metabolism, pathology)
• Macrophages (drug effects, metabolism)
• Male
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Rats, Wistar
• Recombinant Proteins (pharmacology)
• Signal Transduction (drug effects)