Knockout of Wdr1 results in cardiac hypertrophy and impaired cardiac function in adult mouse heart

Huang, Xiaotong; Li, Ziyi; Hu, Jisheng; Yang, Zihao; Liu, Zhongying; Zhang, Tongcun; Zhang, Chenxi; Yuan, Baiyin

doi:10.1016/j.gene.2019.02.023

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…The mice on AMLN diet showed reduced expression of Nppa and Ankrd1 RNA compared to those on LFD, which was dose-dependently restored with BI9774 treatment (Figure 6E). Other genes found to play a role in hypertrophy including Cyp46a1 , Nfatc1 , Ppargc1a , and Wdr1 showed no significant differences with treatment (Supplementary Figure 3B) (Santolini et al, 2018), (Molkentin, 2004), (Aihara et al, 2000), (Song et al, 2015), (Huang et al, 2019).…”

Section: Resultsmentioning

confidence: 98%

Direct β1/ β2 AMPK activation reduces liver steatosis but not fibrosis in a mouse model of non-alcoholic steatohepatitis

Mather,

Boland,

Rivers

et al. 2024

Preprint

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Abstract5’AMP-activated protein kinase (AMPK) activators show potential for treating Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) due to their inhibiting effects on fatty acid and cholesterol synthesis. The absence of treatments for NASH, and its propensity for progression to severe disease, lead us to identify and characterize BI9774, a small molecule AMPK activator, which we used to evaluate this potential, including its ability to reduce the NASH specific qualities of fibrosis and inflammation in a preclinical study.MaleLepob/Lepobmice on a control or NASH inducing (AMLN) diet, with liver fibrosis were given BI9774 or vehicle for 6 weeks while metabolic and NASH endpoints were evaluated.BI9774 treatment decreased plasma ALT, terminal liver weight, and liver lipids. RNA expression of collagen-related genes decreased, although collagen protein and inflammation remained unaltered. We also observed increased heart weight and glycogen levels, and increased expression of genes associated with cardiac hypertrophy.AMPK activation improved many metabolic endpoints, but lack of significant improvement in liver fibrosis and negative cardiac effects suggest systemic AMPK activation is not an ideal NASH therapy. Reductions in steatosis and fibrosis-related genes indicate that, with extended treatment, a liver specific AMPK activator has potential to resolve hepatic fibrosis.Summary StatementFatty liver disease affects up to 30 percent of adults worldwide with 30% of patients progressing to more sever liver disease. AMPK activation can help reduce liver fat.

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Section: Resultsmentioning

confidence: 98%

Direct β1/ β2 AMPK activation reduces liver steatosis but not fibrosis in a mouse model of non-alcoholic steatohepatitis

Mather,

Boland,

Rivers

et al. 2024

Preprint

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“…24,25 The essential and highly conserved role of WDR1 in embryonic heart development and myocardial maintenance highlights the potential to study human cardiac organogenesis via SCP with in vitro cardioids. 21,[26][27][28] Moreover, our proteoCHIP dataset presents the first proteome characterization of cell type specific expression patterns and cellular dynamics in a developing human tissue at single cell resolution.…”

Section: Cell Type-specific Single-cell Clustering Of In Vitro Derive...mentioning

confidence: 99%

An automated workflow for multiplexed single-cell proteomics sample preparation at unprecedented sensitivity

Hartlmayr

Ctortecka

Seth³

et al. 2021

Preprint

105

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The analysis of single cell proteomes has recently become a viable complement to transcript and genomics studies. Proteins are the main driver of cellular functionality and mRNA levels are often an unreliable proxy of such. Therefore, the global analysis of the proteome is essential to study cellular identities. Both multiplexed and label-free mass spectrometry-based approaches with single cell resolution have lately attributed surprising heterogeneity to believed homogenous cell populations. Even though specialized experimental designs and instrumentation have demonstrated remarkable advances, the efficient sample preparation of single cells still lacks behind. Here, we introduce the proteoCHIP, a universal option for single cell proteomics sample preparation at surprising sensitivity and throughput. The automated processing using a commercial system combining single cell isolation and picoliter dispensing, the cellenONE®, allows to reduce final sample volumes to low nanoliters submerged in a hexadecane layer simultaneously eliminating error prone manual sample handling and overcoming evaporation. With this specialized workflow we achieved around 1,000 protein groups per analytical run at remarkable reporter ion signal to noise while reducing or eliminating the carrier proteome. We identified close to 2,000 protein groups across 158 multiplexed single cells from two highly similar human cell types and clustered them based on their proteome. In-depth investigation of regulated proteins readily identified one of the main drivers for tumorigenicity in this cell type. Our workflow is compatible with all labeling reagents, can be easily adapted to custom workflows and is a viable option for label-free sample preparation. The specialized proteoCHIP design allows for the direct injection of label-free single cells via a standard autosampler resulting in the recovery of 30% more protein groups compared to samples transferred to PEG coated vials. We therefore are confident that our versatile, sensitive, and automated sample preparation workflow will be easily adoptable by non-specialized groups and will drive biological applications of single cell proteomics.

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“…Y-27632 [ 19 ], an inhibitor of ROCK, can reduce the levels of phosphorylated cofilin-2 through the inhibition of ROCK activity, which attenuates endothelin-1-induced neonatal cardiomyocyte hypertrophy, whereas this is achieved in ginseng ( Panax quinquefolius ) [ 62 ] through inhibition of p115Rho guanine nucleotide exchange factor (GEF) activity, which inhibits leptin-induced cardiac hypertrophy. In addition, WD-repeat domain 1 (WDR1), a major cofactor of the ADF/cofilin, has been reported to protect myocardium from myocardial hypertrophic stimuli [ 13 ].…”

Section: Abps In Cardiac Hypertrophymentioning

confidence: 99%

“…Actin is involved in the formation of sarcomeres in cardiomyocytes [ 12 ]. The straight and uniform sarcomeric F-actin is critical for the contractile function of muscle [ 13 ]. In addition, actin assembly is thought to be related with autophagy [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Actin-Binding Proteins in Cardiac Hypertrophy

Pan

Wang

Liu

et al. 2022

Cells

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The heart reacts to a large number of pathological stimuli through cardiac hypertrophy, which finally can lead to heart failure. However, the molecular mechanisms of cardiac hypertrophy remain elusive. Actin participates in the formation of highly differentiated myofibrils under the regulation of actin-binding proteins (ABPs), which provides a structural basis for the contractile function and morphological change in cardiomyocytes. Previous studies have shown that the functional abnormality of ABPs can contribute to cardiac hypertrophy. Here, we review the function of various actin-binding proteins associated with the development of cardiac hypertrophy, which provides more references for the prevention and treatment of cardiomyopathy.

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Knockout of Wdr1 results in cardiac hypertrophy and impaired cardiac function in adult mouse heart

Cited by 6 publications

References 34 publications

Direct β1/ β2 AMPK activation reduces liver steatosis but not fibrosis in a mouse model of non-alcoholic steatohepatitis

Direct β1/ β2 AMPK activation reduces liver steatosis but not fibrosis in a mouse model of non-alcoholic steatohepatitis

An automated workflow for multiplexed single-cell proteomics sample preparation at unprecedented sensitivity

Actin-Binding Proteins in Cardiac Hypertrophy

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