Obestatin ameliorates water retention in chronic heart failure by downregulating renal aquaporin 2 through GPR39, V2R and PPARG signaling

Bao, Li-Zhi; Shen, Ming; Qudirat, Hannisa; Shi, Jianbo; Su, Ting; Song, Jingwen; Wang, Zhongkai; Zhao, Xianxian; Jing, Qing; Zheng, Xiaojiao; Guo, Zhian

doi:10.1016/j.lfs.2019.05.049

Cited by 6 publications

(1 citation statement)

References 41 publications

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“…Therefore, in our research, we further investigated the TF–gene interactions to detect the transcriptional regulators of the robust DEGs. Among the seven identified significant TFs, MEF2A ( 53 ) and PPARG ( 54 ) have been reported to play a role in cardiac remodeling and water retention in HF, respectively. Liu et al found that suppressing expression of TEAD1, the Hippo signaling effector, could activate the necroptotic pathway and induce massive cardiomyocyte necroptosis, ultimately leading to impaired cardiac function ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes and transcription factor regulatory network for heart failure using RNA-seq data and robust rank aggregation analysis

Ma²,

Zeng³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundHeart failure (HF) is the end stage of various cardiovascular diseases with a high mortality rate. Novel diagnostic and therapeutic biomarkers for HF are urgently required. Our research aims to identify HF-related hub genes and regulatory networks using bioinformatics and validation assays.MethodsUsing four RNA-seq datasets in the Gene Expression Omnibus (GEO) database, we screened differentially expressed genes (DEGs) of HF using Removal of Unwanted Variation from RNA-seq data (RUVSeq) and the robust rank aggregation (RRA) method. Then, hub genes were recognized using the STRING database and Cytoscape software with cytoHubba plug-in. Furthermore, reliable hub genes were validated by the GEO microarray datasets and quantitative reverse transcription polymerase chain reaction (qRT-PCR) using heart tissues from patients with HF and non-failing donors (NFDs). In addition, R packages “clusterProfiler” and “GSVA” were utilized for enrichment analysis. Moreover, the transcription factor (TF)–DEG regulatory network was constructed by Cytoscape and verified in a microarray dataset.ResultsA total of 201 robust DEGs were identified in patients with HF and NFDs. STRING and Cytoscape analysis recognized six hub genes, among which ASPN, COL1A1, and FMOD were confirmed as reliable hub genes through microarray datasets and qRT-PCR validation. Functional analysis showed that the DEGs and hub genes were enriched in T-cell-mediated immune response and myocardial glucose metabolism, which were closely associated with myocardial fibrosis. In addition, the TF–DEG regulatory network was constructed, and 13 significant TF–DEG pairs were finally identified.ConclusionOur study integrated different RNA-seq datasets using RUVSeq and the RRA method and identified ASPN, COL1A1, and FMOD as potential diagnostic biomarkers for HF. The results provide new insights into the underlying mechanisms and effective treatments of HF.

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Section: Discussionmentioning

confidence: 99%