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FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation
Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1(ΔHBS), which has reduced mitogenic activity) to alleviate CKD and to stu...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561918/ https://www.ncbi.nlm.nih.gov/pubmed/31189876 http://dx.doi.org/10.1038/s41419-019-1696-9 |
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author | Wang, Dezhong Jin, Mengyun Zhao, Xinyu Zhao, Tianyang Lin, Wei He, Zhengle Fan, Miaojuan Jin, Wei Zhou, Jie Jin, Lingwei Zheng, Chao Jin, Hui Zhao, Yushuo Li, Xiaokun Ying, Lei Wang, Yang Zhu, Guanghui Huang, Zhifeng |
author_facet | Wang, Dezhong Jin, Mengyun Zhao, Xinyu Zhao, Tianyang Lin, Wei He, Zhengle Fan, Miaojuan Jin, Wei Zhou, Jie Jin, Lingwei Zheng, Chao Jin, Hui Zhao, Yushuo Li, Xiaokun Ying, Lei Wang, Yang Zhu, Guanghui Huang, Zhifeng |
author_sort | Wang, Dezhong |
collection | PubMed |
description | Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1(ΔHBS), which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1(ΔHBS) exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1(WT)) in renal tissues. RNA-seq analysis revealed that FGF1(ΔHBS) inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1(ΔHBS) prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1(ΔHBS) on oxidative stress and inflammation were mediated by activation of the GSK-3β/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1(ΔHBS). This finding expands the potential uses of FGF1(ΔHBS) for the treatment of various kinds of CKD associated with oxidative stress and inflammation. |
format | Online Article Text |
id | pubmed-6561918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65619182019-06-21 FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation Wang, Dezhong Jin, Mengyun Zhao, Xinyu Zhao, Tianyang Lin, Wei He, Zhengle Fan, Miaojuan Jin, Wei Zhou, Jie Jin, Lingwei Zheng, Chao Jin, Hui Zhao, Yushuo Li, Xiaokun Ying, Lei Wang, Yang Zhu, Guanghui Huang, Zhifeng Cell Death Dis Article Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1(ΔHBS), which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1(ΔHBS) exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1(WT)) in renal tissues. RNA-seq analysis revealed that FGF1(ΔHBS) inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1(ΔHBS) prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1(ΔHBS) on oxidative stress and inflammation were mediated by activation of the GSK-3β/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1(ΔHBS). This finding expands the potential uses of FGF1(ΔHBS) for the treatment of various kinds of CKD associated with oxidative stress and inflammation. Nature Publishing Group UK 2019-06-12 /pmc/articles/PMC6561918/ /pubmed/31189876 http://dx.doi.org/10.1038/s41419-019-1696-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Dezhong Jin, Mengyun Zhao, Xinyu Zhao, Tianyang Lin, Wei He, Zhengle Fan, Miaojuan Jin, Wei Zhou, Jie Jin, Lingwei Zheng, Chao Jin, Hui Zhao, Yushuo Li, Xiaokun Ying, Lei Wang, Yang Zhu, Guanghui Huang, Zhifeng FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation |
title | FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation |
title_full | FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation |
title_fullStr | FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation |
title_full_unstemmed | FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation |
title_short | FGF1(ΔHBS) ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation |
title_sort | fgf1(δhbs) ameliorates chronic kidney disease via pi3k/akt mediated suppression of oxidative stress and inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561918/ https://www.ncbi.nlm.nih.gov/pubmed/31189876 http://dx.doi.org/10.1038/s41419-019-1696-9 |
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