{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":52,"searchCount":0},"additional":{"omics_type":["Unknown"],"volume":["10(6)"],"submitter":["Wang D"],"pubmed_abstract":["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<sup>ΔHBS</sup>, which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1<sup>ΔHBS</sup> exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1<sup>WT</sup>) in renal tissues. RNA-seq analysis revealed that FGF1<sup>ΔHBS</sup> inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1<sup>ΔHBS</sup> 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<sup>ΔHBS</sup> 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<sup>ΔHBS</sup>. This finding expands the potential uses of FGF1<sup>ΔHBS</sup> for the treatment of various kinds of CKD associated with oxidative stress and inflammation."],"journal":["Cell death & disease"],"pagination":["464"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6561918"],"repository":["biostudies-literature"],"pubmed_title":["FGF1<sup>ΔHBS</sup> ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation."],"pmcid":["PMC6561918"],"pubmed_authors":["Jin W","Wang D","Lin W","Fan M","Zhao T","Zhu G","Zhao Y","Zhao X","Ying L","Li X","Jin H","He Z","Huang Z","Jin M","Zheng C","Wang Y","Zhou J","Jin L"],"view_count":["52"],"additional_accession":[]},"is_claimable":false,"name":"FGF1<sup>ΔHBS</sup> ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation.","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<sup>ΔHBS</sup>, which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1<sup>ΔHBS</sup> exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1<sup>WT</sup>) in renal tissues. RNA-seq analysis revealed that FGF1<sup>ΔHBS</sup> inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1<sup>ΔHBS</sup> 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<sup>ΔHBS</sup> 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<sup>ΔHBS</sup>. This finding expands the potential uses of FGF1<sup>ΔHBS</sup> for the treatment of various kinds of CKD associated with oxidative stress and inflammation.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2024-11-19T20:02:41.709Z","creation":"2019-07-24T07:15:50Z"},"accession":"S-EPMC6561918","cross_references":{"pubmed":["31189876"],"doi":["10.1038/s41419-019-1696-9"]}}