MiR‐26a‐5p alleviates cardiac hypertrophy and dysfunction via targeting ADAM17

Shi, Hongtao; Li, Hao; Zhang, Fan; Xue, Honghong; Zhang, Yanan; Han, Qinghua

doi:10.1002/cbin.11685

Cited by 17 publications

(14 citation statements)

References 37 publications

(48 reference statements)

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“…For example, Shi et al. found that miR-26a-5p alleviated cardiac hypertrophy and dysfunction by targeting ADAM17 [ 27 ]. In addition, miR-26a-5p has been reported to play crucial roles in multiple neoplastic diseases [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation

Chen

Zhou

2022

Renal Failure

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Sepsis-induced acute kidney injury (AKI) is a common and life-threatening complication in hospitalized and critically ill patients and has unacceptable morbidity and mortality rates. However, effective approaches for the diagnosis and treatment of septic AKI are still lacking. Here, we demonstrated significant increases in the miR-26a-5p levels in renal tubular cells of LPS-induced septic AKI models both in vivo and in vitro . Mechanistically, we provided evidence of the involvement of NF-κB in miR-26a-5p induction. LPS treatment of renal tubular cells led to the activation of NF-κB, and inhibition of NF-κB by TPCA-1 prevented the induction of miR-26a-5p. These results indicated that NF-κB was a key upstream factor for the induction of miR-26a-5p in septic AKI. Anti-miR-26a-5p enhanced the expression of IL-6 at both the protein and mRNA levels following LPS treatment. Furthermore, our luciferase microRNA target reporter assay verified that IL-6 is a direct target of miR-26a-5p. Blocking miR-26a-5p promoted renal inflammation and worsened kidney injury. Thus, our study indicated that the miR-26a-5p/IL-6 axis can alleviate sepsis-induced acute kidney injury by inhibiting renal inflammation. This mechanism may represent a therapeutic target for septic AKI.

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Section: Discussionmentioning

confidence: 99%

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation

Chen

Zhou

2022

Renal Failure

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“…Interestingly, delivery of miR-29a-3p has a beneficial effect in myocardial injury ( Ren et al, 2021 ) and cardiac hypertrophy ( Xie et al, 2020 ). Similarly, the hsa-mir-26a/b-5p was highly expressed in cardiac hypertrophy ( Tang et al, 2020 ) and promoted myocardial infarction-induced cell death ( Jung et al, 2021 ), yet overexpression of miR-26a/b attenuated cardiac fibrosis ( Tang et al, 2017 ; Wang et al, 2019 ) and alleviated cardiac hypertrophy and dysfunction ( Shi et al, 2021 ). Lastly, the hsa-mir-124-3p was reported to promote cardiac fibroblast activation and proliferation ( Zhu et al, 2021 ), and its inhibition protects against acute myocardial infarction by suppressing cardiomyocyte apoptosis ( Hu et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Long-term culture of patient-derived cardiac organoids recapitulated Duchenne muscular dystrophy cardiomyopathy and disease progression

Marini

Marino

Aliberti

et al. 2022

Front. Cell Dev. Biol.

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Duchenne Muscular Dystrophy (DMD) is an X-linked neuromuscular disease which to date is incurable. The major cause of death is dilated cardiomyopathy however, its pathogenesis is unclear as existing cellular and animal models do not fully recapitulate the human disease phenotypes. In this study, we generated cardiac organoids from patient-derived induced pluripotent stem cells (DMD-COs) and isogenic-corrected controls (DMD-Iso-COs) and studied if DMD-related cardiomyopathy and disease progression occur in the organoids upon long-term culture (up to 93 days). Histological analysis showed that DMD-COs lack initial proliferative capacity, displayed a progressive loss of sarcoglycan localization and high stress in endoplasmic reticulum. Additionally, cardiomyocyte deterioration, fibrosis and aberrant adipogenesis were observed in DMD-COs over time. RNA sequencing analysis confirmed a distinct transcriptomic profile in DMD-COs which was associated with functional enrichment in hypertrophy/dilated cardiomyopathy, arrhythmia, adipogenesis and fibrosis pathways. Moreover, five miRNAs were identified to be crucial in this dysregulated gene network. In conclusion, we generated patient-derived cardiac organoid model that displayed DMD-related cardiomyopathy and disease progression phenotypes in long-term culture. We envision the feasibility to develop a more complex, realistic and reliable in vitro 3D human cardiac-mimics to study DMD-related cardiomyopathies.

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“…In this study, we also constructed a gene-miRNA regulatory network, and four miRNAs (mir-26a-5p, mir-1343-3p, mir-129-2-3p, and mir-124-3p) were identified because of their interaction at least with four hub DEARGs. Mir-26a-5p can alleviate cardiac hypertrophy and dysfunction ( Shi et al, 2021 ) and protect against myocardial ischemia/reperfusion injury ( Xing et al, 2020 ). Mir-1343-3p plays a significant role in the development of human cancers such as lung cancer ( Zhang et al, 2020 ), colorectal carcinoma ( Bhat et al, 2022 ), and hepatocellular carcinoma ( Mou and Sun, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive molecular analyses of an autoimmune-related gene predictive model and immune infiltrations using machine learning methods in moyamoya disease

Han

Zhang

et al. 2022

Front. Mol. Biosci.

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Background: Growing evidence suggests the links between moyamoya disease (MMD) and autoimmune diseases. However, the molecular mechanism from genetic perspective remains unclear. This study aims to clarify the potential roles of autoimmune-related genes (ARGs) in the pathogenesis of MMD.Methods: Two transcription profiles (GSE157628 and GSE141025) of MMD were downloaded from GEO databases. ARGs were obtained from the Gene and Autoimmune Disease Association Database (GAAD) and DisGeNET databases. Differentially expressed ARGs (DEARGs) were identified using “limma” R packages. GO, KEGG, GSVA, and GSEA analyses were conducted to elucidate the underlying molecular function. There machine learning methods (LASSO logistic regression, random forest (RF), support vector machine-recursive feature elimination (SVM-RFE)) were used to screen out important genes. An artificial neural network was applied to construct an autoimmune-related signature predictive model of MMD. The immune characteristics, including immune cell infiltration, immune responses, and HLA gene expression in MMD, were explored using ssGSEA. The miRNA-gene regulatory network and the potential therapeutic drugs for hub genes were predicted.Results: A total of 260 DEARGs were identified in GSE157628 dataset. These genes were involved in immune-related pathways, infectious diseases, and autoimmune diseases. We identified six diagnostic genes by overlapping the three machine learning algorithms: CD38, PTPN11, NOTCH1, TLR7, KAT2B, and ISG15. A predictive neural network model was constructed based on the six genes and presented with great diagnostic ability with area under the curve (AUC) = 1 in the GSE157628 dataset and further validated by GSE141025 dataset. Immune infiltration analysis showed that the abundance of eosinophils, natural killer T (NKT) cells, Th2 cells were significant different between MMD and controls. The expression levels of HLA-A, HLA-B, HLA-C, HLA-DMA, HLA-DRB6, HLA-F, and HLA-G were significantly upregulated in MMD. Four miRNAs (mir-26a-5p, mir-1343-3p, mir-129-2-3p, and mir-124-3p) were identified because of their interaction at least with four hub DEARGs.Conclusion: Machine learning was used to develop a reliable predictive model for the diagnosis of MMD based on ARGs. The uncovered immune infiltration and gene-miRNA and gene-drugs regulatory network may provide new insight into the pathogenesis and treatment of MMD.

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MiR‐26a‐5p alleviates cardiac hypertrophy and dysfunction via targeting ADAM17

Cited by 17 publications

References 37 publications

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation

Long-term culture of patient-derived cardiac organoids recapitulated Duchenne muscular dystrophy cardiomyopathy and disease progression

Comprehensive molecular analyses of an autoimmune-related gene predictive model and immune infiltrations using machine learning methods in moyamoya disease

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