Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Longwei, Wang, Huiyan, Xie, Junjun, Chen, Zilu, Li, Xiaokun, Niu, Jianlou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496364/
https://www.ncbi.nlm.nih.gov/pubmed/28676059
http://dx.doi.org/10.1186/s12896-017-0368-z
_version_ 1783247963673329664
author Zhao, Longwei
Wang, Huiyan
Xie, Junjun
Chen, Zilu
Li, Xiaokun
Niu, Jianlou
author_facet Zhao, Longwei
Wang, Huiyan
Xie, Junjun
Chen, Zilu
Li, Xiaokun
Niu, Jianlou
author_sort Zhao, Longwei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5496364
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-54963642017-07-05 Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice Zhao, Longwei Wang, Huiyan Xie, Junjun Chen, Zilu Li, Xiaokun Niu, Jianlou BMC Biotechnol Research Article 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. BioMed Central 2017-07-04 /pmc/articles/PMC5496364/ /pubmed/28676059 http://dx.doi.org/10.1186/s12896-017-0368-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhao, Longwei
Wang, Huiyan
Xie, Junjun
Chen, Zilu
Li, Xiaokun
Niu, Jianlou
Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice
title Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice
title_full Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice
title_fullStr Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice
title_full_unstemmed Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice
title_short Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice
title_sort potent long-acting rhfgf21 analog for treatment of diabetic nephropathy in db/db and dio mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496364/
https://www.ncbi.nlm.nih.gov/pubmed/28676059
http://dx.doi.org/10.1186/s12896-017-0368-z
work_keys_str_mv AT zhaolongwei potentlongactingrhfgf21analogfortreatmentofdiabeticnephropathyindbdbanddiomice
AT wanghuiyan potentlongactingrhfgf21analogfortreatmentofdiabeticnephropathyindbdbanddiomice
AT xiejunjun potentlongactingrhfgf21analogfortreatmentofdiabeticnephropathyindbdbanddiomice
AT chenzilu potentlongactingrhfgf21analogfortreatmentofdiabeticnephropathyindbdbanddiomice
AT lixiaokun potentlongactingrhfgf21analogfortreatmentofdiabeticnephropathyindbdbanddiomice
AT niujianlou potentlongactingrhfgf21analogfortreatmentofdiabeticnephropathyindbdbanddiomice