Diabetes Metab J.  2020 Aug;44(4):566-580. 10.4093/dmj.2019.0089.

Therapeutic Effects of Fibroblast Growth Factor-21 on Diabetic Nephropathy and the Possible Mechanism in Type 1 Diabetes Mellitus Mice

Affiliations
  • 1Ruian Center of the Chinese-American Institute for Diabetic Complications, the Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2Cancer Center, the First Hospital of Jilin University, Changchun, China.
  • 3Biological Engineering Department, School of Life Science, Anhui Medical University, Hefei, China.
  • 4The Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.

Abstract

Background

Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN.

Methods

Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups.

Results

The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression.

Conclusion

Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.


Keyword

AMP-activated protein kinases; Diabetes mellitus, type 1; Diabetic nephropathies; Fibroblast growth factor 21; Fibrosis; Inflammation; Sirtuin 1
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