Affiliation:
1. Department of Cardiology, Jinhua People's Hospital, Jinhua, Zhejiang, China
2. Department of Blood Donation Service,
Central Blood Station of Jinhua, Jinhua, Zhejiang, China
3. Department of IVF, Jinhua People's Hospital, Jinhua,
Zhejiang, China
4. Department of Endocrinology, Jinhua People's Hospital, Jinhua, Zhejiang, China
5. Department of
Ultrasound in Medicine, Jinhua People's Hospital, Jinhua, Zhejiang, China
Abstract
Background::
Dapagliflozin is commonly used to treat type 2 diabetes mellitus
(T2DM). However, research into the specific anti-T2DM mechanisms of dapagliflozin remains
scarce.
Objective::
This study aimed to explore the underlying mechanisms of dapagliflozin against
T2DM.
Methods::
Dapagliflozin-associated targets were acquired from CTD, SwissTargetPrediction,
and SuperPred. T2DM-associated targets were obtained from GeneCards and DigSee. VennDiagram
was used to obtain the overlapping targets of dapagliflozin and T2DM. GO and KEGG
analyses were performed using clusterProfiler. A PPI network was built by STRING database
and Cytoscape, and the top 30 targets were screened using the degree, maximal clique centrality
(MCC), and edge percolated component (EPC) algorithms of CytoHubba. The top 30 targets
screened by the three algorithms were intersected with the core pathway-related targets to obtain
the key targets. DeepPurpose was used to evaluate the binding affinity of dapagliflozin with the
key targets.
Results::
In total, 155 overlapping targets of dapagliflozin and T2DM were obtained. GO and
KEGG analyses revealed that the targets were primarily enriched in response to peptide, membrane
microdomain, protein serine/threonine/tyrosine kinase activity, PI3K-Akt signaling pathway,
MAPK signaling pathway, and AGE-RAGE signaling pathway in diabetic complications.
AKT1, PIK3CA, NOS3, EGFR, MAPK1, MAPK3, HSP90AA1, MTOR, RELA, NFKB1,
IKBKB, ITGB1, and TP53 were the key targets, mainly related to oxidative stress, endothelial
function, and autophagy. Through the DeepPurpose algorithm, AKT1, HSP90AA1, RELA,
ITGB1, and TP53 were identified as the top 5 anti-targets of dapagliflozin.
Conclusion::
Dapagliflozin might treat T2DM mainly by targeting AKT1, HSP90AA1, RELA,
ITGB1, and TP53 through PI3K-Akt signaling.
Publisher
Bentham Science Publishers Ltd.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献