Atypical ALPK2 kinase is not essential for cardiac development and function

Bogomolovas, Julius; Feng, Wei; Yu, Matthew Daniel; Huang, Serena; Zhang, Lunfeng; Trexler, Christa; Gu, Yusu; Spinozzi, Simone; Chen, Ju

doi:10.1152/ajpheart.00249.2020

Cited by 5 publications

(2 citation statements)

References 37 publications

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“…In turn, ALPK2 and CASQ1 were detected in pluripotent stem cell-derived lineages. The expression of the former was noted in cardiac cell development, while the latter was implicated in neurogenic differentiation [45][46][47]. The presence of products of two further genes, SLC4A10 and SERPINE1, was detected in the content of mesenchymal stem cell-derived exosomes [48,49].…”

Section: Discussionmentioning

confidence: 99%

Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

Jankowski

Kaczmarek

Wąsiatycz

et al. 2021

IJMS

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Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells’ application in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

Jankowski

Kaczmarek

Wąsiatycz

et al. 2021

IJMS

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“…Due to the close genetic background of mice, we can obtain stable experimental results. With the development of genome editing technology, various disease models, such as those of Parkinson's disease [44], glaucoma [45], and heart disease [46], have been established using mice. Therefore, mouse models will continue to be useful for the development of drug discovery research.…”

Section: Mus Musculus (Mice)mentioning

confidence: 99%

State-of-the-Art Technology of Model Organisms for Current Human Medicine

et al. 2020

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Since the 1980s, molecular biology has been used to investigate medical field mechanisms that still require the use of crude biological materials in order to achieve their necessary goals. Transcription factor-induced pluripotent stem cells are used in regenerative medicine to screen drugs and to support lost tissues. However, these cells insufficiently reconstruct whole organs and require various intact cells, such as damaged livers and diabetic pancreases. For efficient gene transfer in medical use, virally mediated gene transfers are used, although immunogenic issues are investigated. To obtain efficient detective and diagnostic power in intractable diseases, biological tools such as roundworms and zebrafish have been found to be useful for high-throughput screening (HST) and diagnosis. Taken together, this biological approach will help to fill the gaps between medical needs and novel innovations in the field of medicine.

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ALPK2 prevents cardiac diastolic dysfunction in heart failure with preserved ejection fraction

Yoshida,

Inukai

et al. 2024

The FASEB Journal

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Protein phosphorylation, controlled by protein kinases, is central to regulating various pathophysiological processes, including cardiac systolic function. The dysregulation of protein kinase activity plays a significant role in the pathogenesis of cardiac systolic dysfunction. While cardiac contraction mechanisms are well documented, the mechanisms underlying cardiac diastole remain elusive. This gap persists owing to the historical focus on systolic dysfunction in heart failure research. Recently, heart failure with preserved ejection fraction (HFpEF), an age‐related disease characterized by cardiac diastolic dysfunction, has emerged as a major public health concern. However, its underlying mechanism remains unclear. In this study, we investigated cardiac protein kinases by analyzing the gene expression of 518 protein kinases in human tissues. We identified alpha‐kinase 2 (ALPK2) as a novel cardiac‐specific atypical kinase and generated tamoxifen‐inducible, cardiomyocyte‐specific Alpk2‐knockout mice and Alpk2‐overexpressing mice. Alpk2 deficiency did not affect cardiac systolic dysfunction in the myocardial infarction model or the pressure‐overload‐induced heart failure model. Notably, cardiomyocyte‐specific Alpk2 deficiency exacerbated cardiac diastolic dysfunction induced by aging and in the HFpEF model. Conversely, Alpk2 overexpression increased the phosphorylation of tropomyosin 1, a major regulator that binds myosin to actin, and mitigated cardiac stiffness in HFpEF. This study provides novel evidence that ALPK2 represents a potential therapeutic target for cardiac diastolic dysfunction in HFpEF and age‐related cardiac impairments.

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Atypical ALPK2 kinase is not essential for cardiac development and function

Cited by 5 publications

References 37 publications

Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

State-of-the-Art Technology of Model Organisms for Current Human Medicine

ALPK2 prevents cardiac diastolic dysfunction in heart failure with preserved ejection fraction

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