Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling

Gao, Weinian; Guo, Na; Zhao, Sen; Chen, Ziying; Zhang, Wenli; Yan, Fang; Liao, Haojie; Chi, Kui

doi:10.1042/bsr20200669

Cited by 15 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CPA4 expression inhibited the tumor proliferation and regulated the expression of stem cell characteristics in hepatocellular carcinoma ( 22 ). Nevertheless, CPA4 was found to be a key regulator of cardiac hypertrophy through activating PI3K-AKT-mTOR signaling and may serve as a promising therapy target for hypertrophic cardiac diseases ( 23 ). CPA6 could promote cell proliferation and migration through regulating the AKT signaling pathway in hepatocellular carcinoma ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Carboxypeptidase N2 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma

Zhang

Chen

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Carboxypeptidase N2 (CPN2) is a plasma metallo-protease that cleaves basic amino acids from the C-terminal of peptides and proteins. Emerging evidence showed that carboxypeptidases perform many diverse functions in the body and play key roles in tumorigenesis. However, the clinical significance and biological functions of CPN2 in lung adenocarcinoma remain unclear. Our study aimed to explore the potential role and functions of CPN2 in lung adenocarcinoma. The results showed that the transcription level of CPN2 was significantly increased in the tumor tissues of lung adenocarcinoma patients compared to the adjacent normal tissues in The Cancer Genome Atlas cohort (P < 0.05). The survival plots showed that the overall survival of patients with a high expression of CPN2 was significantly lower than that of patients with a low expression of CPN2, both in the Kaplan–Meier database and the clinical sample cohort (P < 0.05). The tissue microarray analysis found that CPN2 protein expression was significantly positively correlated with node status and tumor stage as well as tumor malignancy (P < 0.05). Further univariate and multivariate Cox regression analyses showed that CPN2 may act as an independent prognostic factor in patients with lung adenocarcinoma (P < 0.05). In addition, the analysis of co-expression genes from LinkedOmics showed that CPN2 was positively associated with many genes of fibrillar collagen family members and the PI3K-Akt pathway. The gene set enrichment analysis showed that a higher expression of CPN2 may participate in mTOR, TGF-BETA, NOTCH, TOLL-like-receptor, WNT, and MAPK signaling pathway in lung adenocarcinoma. Notably, the knockdown of CPN2 significantly inhibited the ability of cell proliferation, clone formation, invasion, and migration. Our findings suggested that the upregulation of CPN2 is associated with a worse clinical outcome in lung adenocarcinoma and cancer-related pathways, which laid the foundation for further research on CPN2 during carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Carboxypeptidase N2 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma

Zhang

Chen

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Existing reports indicate that histone modification and DNA methylation are involved in the occurrence and development of myocardial hypertrophy ( 37 , 38 ). The occurrence and development of cardiac hypertrophy is also accompanied by the abnormal activation of a large number of important signaling pathways ( 5 , 39 , 40 ). Consequently, there is an increased level of interest in how key signaling pathways participate in the epigenetic regulation of cardiac hypertrophy ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, it was shown that the imbalance in the modification of histone H3K9ac, a process mediated by histone acetylases (HATs), is involved in phenylephrine (PE)-induced cardiomyocyte hypertrophy ( 4 ). Several studies have shown that cardiac hypertrophy can be induced by the activation of multiple signaling pathways ( 5 – 8 ). The extracellular signal-regulated protein kinase (ERK) signaling pathway is considered to play a particularly important role in regulating pathological cardiac hypertrophy ( 9 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy

Mao

Chang

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

Cardiomyocyte hypertrophy is a compensatory phase of chronic heart failure that is induced by the activation of multiple signaling pathways. The extracellular signal-regulated protein kinase (ERK) signaling pathway is an important regulator of cardiomyocyte hypertrophy. In our previous study, it was demonstrated that phenylephrine (PE)-induced cardiomyocyte hypertrophy involves the hyperacetylation of histone H3K9ac by P300/CBP-associated factor (PCAF). However, the upstream signaling pathway has yet to be fully identified. In the present study, the role of the extracellular signal-regulated protein kinase (ERK)1/2 signaling pathway in PE-induced cardiomyocyte hypertrophy was investigated. The mice cardiomyocyte hypertrophy model was successfully established by treating cells with PE in vitro. The results showed that phospho-(p-)ERK1/2 interacted with PCAF and modified the pattern of histone H3K9ac acetylation. An ERK inhibitor (U0126) and/or a histone acetylase inhibitor (anacardic acid; AA) attenuated the overexpression of phospho-ERK1/2 and H3K9ac hyperacetylation by inhibiting the expression of PCAF in PE-induced cardiomyocyte hypertrophy. Moreover, U0126 and/or AA could attenuate the overexpression of several biomarker genes related to cardiac hypertrophy (myocyte enhancer factor 2C, atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain) and prevented cardiomyocyte hypertrophy. These results revealed a novel mechanism in that AA protects against PE-induced cardiomyocyte hypertrophy in mice via the ERK1/2 signaling pathway, and by modifying the acetylation of H3K9ac. These findings may assist in the development of novel methods for preventing and treating hypertrophic cardiomyopathy.

show abstract

“…However, the multi-target characteristics of TCM monomers suggest that PU has multiple therapeutic targets (37). Numerous signaling pathways are associated with the pathophysiology of MH, including the 5'AMP-activated protein kinase/mTOR (38), PI3K/AKT/mTOR (39) and insulin-like growth factor 1/PI3K/AKT (40) signaling pathways. Therefore, the exploration of the mechanism of PU on MH to achieve the effect of precise treatment is urgent.…”

Section: Introductionmentioning

confidence: 99%

Puerarin attenuates isoproterenol‑induced myocardial hypertrophy via inhibition of the Wnt/β‑catenin signaling pathway

Wang

et al. 2022

Mol Med Rep

View full text Add to dashboard Cite

Myocardial hypertrophy (MH) is an independent risk factor for cardiovascular disease, which in turn lead to arrhythmia or heart failure. Therefore, attention must be paid to formulation of therapeutic strategies for MH. Puerarin is a key bioactive ingredient isolated from Pueraria genera of plants that is beneficial for the treatment of MH. However, its molecular mechanism of action has not been fully determined.In the present study, 40 µM puerarin was demonstrated to be a safe dose for human AC16 cells using Cell Counting Kit-8 assay. The protective effects of puerarin against MH were demonstrated in AC16 cells stimulated with isoproterenol (ISO). These effects were characterized by a significant decrease in surface area of cells (assessed using fluorescence staining) and mRNA and protein expression levels of MH-associated biomarkers, including atrial and brain natriuretic peptide, assessed using reverse transcription-quantitative PCR and western blotting, as well as β-myosin heavy chain mRNA expression levels. Mechanistically, western blotting demonstrated that puerarin inhibited activation of the Wnt signaling pathway. Puerarin also significantly decreased phosphorylation of p65; this was mediated via crosstalk between the Wnt and NF-κB signaling pathways. An inhibitor (Dickkopf-1) and activator (IM-12) of the Wnt signaling pathway were used to demonstrate that puerarin-mediated effects alleviated ISO-induced MH via the Wnt signaling pathway. The results of the present study demonstrated that puerarin pre-treatment may be a potential therapeutic strategy for preventing ISO-induced MH and managing MH in the future.

show abstract

Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling

Cited by 15 publications

References 33 publications

Carboxypeptidase N2 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma

Carboxypeptidase N2 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma

Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy

Puerarin attenuates isoproterenol‑induced myocardial hypertrophy via inhibition of the Wnt/β‑catenin signaling pathway

Contact Info

Product

Resources

About