FGF1ΔHBS ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation
| Autor: | Tianyang Zhao, Zhengle He, Xiaokun Li, Yushuo Zhao, Hui Jin, Zhou Jie, Chao Zheng, Yang Wang, Lei Ying, Meng-Yun Jin, Lingwei Jin, Miaojuan Fan, Xinyu Zhao, Wei Jin, Guanghui Zhu, Wei Lin, Zhifeng Huang, Dezhong Wang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Immunology Inflammation Pharmacology medicine.disease_cause Nephropathy Diabetic nephropathy 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine ASK1 lcsh:QH573-671 Protein kinase B PI3K/AKT/mTOR pathway lcsh:Cytology business.industry Cell Biology medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis medicine.symptom business Oxidative stress Kidney disease |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 6, Pp 1-14 (2019) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1696-9 |
| Popis: | 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 (FGF1ΔHBS, which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1ΔHBS exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1WT) in renal tissues. RNA-seq analysis revealed that FGF1ΔHBS inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1ΔHBS 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 FGF1ΔHBS 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 FGF1ΔHBS. This finding expands the potential uses of FGF1ΔHBS for the treatment of various kinds of CKD associated with oxidative stress and inflammation. |
| Databáze: | OpenAIRE |
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