JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice.

BMC Biotechnology 2017 July 5
BACKGROUND: Fibroblast growth factor 21 (FGF21) is an endocrine-acting hormone that has the potential to treat diabetic nephropathy. However, development of FGF21 into a therapeutic has been hindered due to its low intrinsic bio-stability. In our previous study, we have developed a recombinant human FGF21 (rhFGF21) variant by site-directed mutagenesis and solid-phase PEGylation, which retained its biological function. The aim of this study is to elucidate whether the therapeutic effect of PEGylated rhFGF21 (PEG-rhFGF21) on diabetic nephropathy in DIO (diet induced obesity) mice is more significant than rhFGF21 in vivo.

RESULTS: After administration with rhFGF21 and PEG-rhFGF21 for 2 months, biochemical data and histological examination showed that PEG-rhFGF21 significantly lowered lipid levels in the kidney, decreased urine albumin/creatinine ratio (ACR) and improved mesangial expansion, demonstrating that PEG-rhFGF21 was more efficacious in ameliorating functional and morphological abnormalities induced by diabetic nephropathy in db/db and DIO mice.

CONCLUSIONS: Our findings suggest that PEG-rhFGF21 treatment is more effective in treating diabetic nephropathy than rhFGF21, through enhancements of systemic metabolic alterations and anti-inflammatory mechanisms. These findings help provide a theoretical basis to develop more long-acting and efficacious protein drugs for diabetic nephropathy.

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