4.7 Article

Investigation into the effect and mechanism of dapagliflozin against renal interstitial fibrosis based on transcriptome and network pharmacology

期刊

INTERNATIONAL IMMUNOPHARMACOLOGY
卷 112, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.intimp.2022.109195

关键词

Renal interstitial fibrosis; Dapagliflozin; Network pharmacology; Inflammation; Apoptosis; Oxidative stress

资金

  1. National Natural Science Founda-tion of China
  2. [81770718]
  3. [82170745]
  4. [82000687]

向作者/读者索取更多资源

Dapagliflozin has been shown to improve renal function and reduce renal interstitial fibrosis (RIF) in a mouse model, independent of blood glucose control. Transcriptome analysis and molecular biology methods suggest that dapagliflozin's therapeutic effect on RIF may be achieved through multiple pathways regulation. Network pharmacology analysis also revealed potential targets of dapagliflozin against RIF.
Background: Renal interstitial fibrosis (RIF) is the final pathway for chronic kidney diseases (CKD) to end-stage renal disease (ESRD). Dapagliflozin, a selective inhibitor of the sodium glucose co-transporter 2, reduced the risk of renal events in non-diabetic CKD patients in the DAPA-CKD trial. However, the effect and mechanism of dapagliflozin on RIF are not very clear. Currently, we evaluate the effects of dapagliflozin on RIF and system-atically explore its mechanism.Methods and Results: Firstly, unilateral ureteral obstruction (UUO) mouse model was established to evaluate effects of dapagliflozin on RIF, and results demonstrated dapagliflozin improved renal function and RIF of UUO mice independent of blood glucose control. Subsequently, transcriptome analysis was performed to explore the potential mechanism of dapagliflozin against RIF, which exhibited the therapeutic effect of dapagliflozin on RIF may be achieved through multiple pathways regulation. Then we verified the potential mechanisms with mo-lecular biology methods, and found that dapagliflozin treatment significantly alleviated inflammation, apoptosis, oxidative stress and mitochondrial injury in kidneys of UUO mice. Furthermore, network pharmacology analysis was used to investigate the potential targets of dapagliflozin against RIF. Moreover, we also applied molecular docking and molecular dynamics simulation to predict the specific binding sites and binding capacity of dapa-gliflozin and hub target. Conclusions: Dapagliflozin had therapeutic effect on RIF independent of blood glucose control, and the protective effects probably mediated by multiple pathways and targets regulation.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据