STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) Inhibits Pathological Cardiac Hypertrophy

Li, Penglong; Liu, Hui; Chen, Guopeng; L, Li; Shi, Hongjie; Nie, Hongyu; Liu, Zhen; Hu, Yufeng; Yang, Juan; Zhang, Peng; Zhang, Xiaojing; She, Zhi‐Gang; Li, Hongliang; Huang, Zan; Zhu, Lihua

doi:10.1161/hypertensionaha.120.14752

Cited by 29 publications

(32 citation statements)

References 39 publications

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“…To gain insights into the mechanisms by which LAPTM5 regulated the MEK-ERK1/2 signaling pathway, we performed mass spectrometry analysis and identified Rac1, a GTP-binding protein. Numerous studies have confirmed that Rac1 is involved in pressure overload-induced heart failure and the MEK-ERK1/2 signaling pathway (30). In our study, Rac1 was found to be the direct target of LAPTM5 in cardiomyocytes, as LAPTM5 overlaps with the Rac1 protein and interacts with each other.…”

Section: Discussionsupporting

confidence: 73%

Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

Guo

Long

Xiao

et al. 2021

Front. Cardiovasc. Med.

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Lysosomal-associated protein transmembrane 5 (LAPTM5) is mainly expressed in immune cells and has been reported to regulate inflammation, apoptosis and autophagy. Although LAPTM5 is expressed in the heart, whether LAPTM5 plays a role in regulating cardiac function remains unknown. Here, we show that the expression of LAPTM5 is dramatically decreased in murine hypertrophic hearts and isolated hypertrophic cardiomyocytes. In this study, we investigated the role of LAPTM5 in pathological cardiac hypertrophy and its possible mechanism. Our results show that LAPTM5 gene deletion significantly exacerbates cardiac remodeling, which can be demonstrated by reduced myocardial hypertrophy, fibrosis, ventricular dilation and preserved ejection function, whereas the opposite phenotype was observed in LAPTM5 overexpression mice. In line with the in vivo results, knockdown of LAPTM5 exaggerated angiotensin II-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes, whereas overexpression of LAPTM5 protected against angiotensin II-induced cardiomyocyte hypertrophy in vitro. Mechanistically, LAPTM5 directly bound to Rac1 and further inhibited MEK-ERK1/2 signaling, which ultimately regulated the development of cardiac hypertrophy. In addition, the antihypertrophic effect of LAPTM5 was largely blocked by constitutively active mutant Rac1 (G12V). In conclusion, our results suggest that LAPTM5 is involved in pathological cardiac hypertrophy and that targeting LAPTM5 has great therapeutic potential in the treatment of pathological cardiac hypertrophy.

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Section: Discussionsupporting

confidence: 73%

Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

Guo

Long

Xiao

et al. 2021

Front. Cardiovasc. Med.

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“…Evidence from Safa et al [ 167 ], Chen et al [ 168 ], Zhou et al [ 169 ], Hu et al [ 170 ], Lou et al [ 171 ], Zhang et al [ 172 ] and Chen et al [ 173 ] study indicated that the expression of CCL22, CCR1, FPR1, KNG1, CRISPLD2, CD38 and GPRC5A were linked with progression of ischemic heart disease. Li et al [ 174 ] showed that STEAP3 expression can be associated with cardiac hypertrophy progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis

Kolur¹,

Vastrad²,

Vastrad

et al. 2021

BMC Cardiovasc Disord

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Introduction Heart failure (HF) is a heterogeneous clinical syndrome and affects millions of people all over the world. HF occurs when the cardiac overload and injury, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental HF as well as to explore active drug molecules. Methods The expression profiling by high throughput sequencing of GSE141910 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which contained 366 samples, including 200 heart failure samples and 166 non heart failure samples. The raw data was integrated to find differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. Gene ontology (GO) and REACTOME enrichment analyses were performed via ToppGene; protein–protein interaction (PPI) networks of the DEGs was constructed based on data from the HiPPIE interactome database; modules analysis was performed; target gene—miRNA regulatory network and target gene—TF regulatory network were constructed and analyzed; hub genes were validated; molecular docking studies was performed. Results A total of 881 DEGs, including 442 up regulated genes and 439 down regulated genes were observed. Most of the DEGs were significantly enriched in biological adhesion, extracellular matrix, signaling receptor binding, secretion, intrinsic component of plasma membrane, signaling receptor activity, extracellular matrix organization and neutrophil degranulation. The top hub genes ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 were identified from the PPI network. Module analysis revealed that HF was associated with adaptive immune system and neutrophil degranulation. The target genes, miRNAs and TFs were identified from the target gene—miRNA regulatory network and target gene—TF regulatory network. Furthermore, receiver operating characteristic (ROC) curve analysis and RT-PCR analysis revealed that ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 might serve as prognostic, diagnostic biomarkers and therapeutic target for HF. The predicted targets of these active molecules were then confirmed. Conclusion The current investigation identified a series of key genes and pathways that might be involved in the progression of HF, providing a new understanding of the underlying molecular mechanisms of HF.

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“…MFAP4 [79], ALOX15 [80], COL1A1 [81], APOA1 [82], PDE5A [83], CX3CR1 [84], THY1 [85], GREM1 [86], FMOD (fibromodulin) [87], NPPA (natriuretic peptide A) [88], LTBP2 [89], LUM (lumican) [90], IL34 [91], NRG1 [92], CXCL14 [93], CXCL10 [94], ACE (angiotensin I converting enzyme) [95], CFTR (ystic fibrosis transmembrane conductance regulator) [96], S100A8 [97], S100A9 [97], HP (haptoglobin) [98] [162], Zhang et al [163] and Chen et al [164] study indicated that the expression of CCL22, CCR1, FPR1, KNG1, CRISPLD2, CD38 and GPRC5A were linked with progression of ischemic heart disease. Li et al [165] showed that STEAP3 expression can be associated with cardiac hypertrophy progression.…”

Section: Discussionmentioning

confidence: 99%

“…[158], Chen et al [159], Zhou et al [160], Hu et al [161], Lou et al [162], Zhang et al [163] and Chen et al [164] study indicated that the expression of CCL22, CCR1, FPR1, KNG1, CRISPLD2, CD38 and GPRC5A were linked with progression of ischemic heart disease. Li et al [165] showed that STEAP3 expression can be associated with cardiac hypertrophy progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis

Vastrad¹,

Tengli

Vastrad³

2021

Preprint

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Heart failure (HF) is a heterogeneous clinical syndrome and affects millions of people all over the world. HF occurs when the cardiac overload and injury, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental HF as well as to explore active drug molecules. The expression profiling by high throughput sequencing of GSE141910 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which contained 366 samples, including 200 heart failure samples and 166 non heart failure samples. The raw data was integrated to find differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. Gene ontology (GO) and REACTOME enrichment analyses were performed via ToppGene; protein-protein interaction (PPI) networks of the DEGs was constructed based on data from the HiPPIE interactome database; modules analysis was performed; target gene - miRNA regulatory network and target gene - TF regulatory network were constructed and analyzed; hub genes were validated; molecular docking studies was performed. A total of 881 DEGs, including 442 up regulated genes and 439 down regulated genes were observed. Most of the DEGs were significantly enriched in biological adhesion, extracellular matrix, signaling receptor binding, secretion, intrinsic component of plasma membrane, signaling receptor activity, extracellular matrix organization and neutrophil degranulation. The top hub genes ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 were identified from the PPI network. Module analysis revealed that HF was associated with adaptive immune system and neutrophil degranulation. The target genes, miRNAs and TFs were identified from the target gene - miRNA regulatory network and target gene - TF regulatory network. Furthermore, receiver operating characteristic (ROC) curve analysis and RT-PCR analysis revealed that ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 might serve as prognostic, diagnostic biomarkers and therapeutic target for HF. The predicted targets of these active molecules were then confirmed. The current investigation identified a series of key genes and pathways that might be involved in the progression of HF, providing a new understanding of the underlying molecular mechanisms of HF.

show abstract

STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) Inhibits Pathological Cardiac Hypertrophy

Cited by 29 publications

References 39 publications

Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis

Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis

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