Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice.

Authors:
Longwei Zhao
Longwei Zhao
School of Pharmacy & Center for Structural Biology
Huiyan Wang
Huiyan Wang
Shandong University
China
Junjun Xie
Junjun Xie
Huazhong Agricultural University
China
Zilu Chen
Zilu Chen
Guangxi Normal University
China
Xiaokun Li
Xiaokun Li
School of Pharmaceutical Sciences
China
Jianlou Niu
Jianlou Niu
School of Pharmacy
China

BMC Biotechnol 2017 07 4;17(1):58. Epub 2017 Jul 4.

School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, China.

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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http://dx.doi.org/10.1186/s12896-017-0368-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496364PMC
July 2017
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