Muscle Cell News Volume 2.16 | May 8 2017

TOP STORY

PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism

BMP2 and TGFβ1 are functional antagonists of pathological remodeling in the arteries, heart, and lung; however, the mechanisms in vascular smooth muscle cells (VSMCs), and their disturbance in pulmonary arterial hypertension, are unclear. Investigators found a pro-proliferative TGFβ1-Stat3-FoxO1 axis in VSMCs, and PPARγ as an inhibitory regulator of TGFβ1-Stat3-FoxO1 and TGFβ1-Smad3/4, by physically interacting with Stat3 and Smad3. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Cnot3 Enhances Human Embryonic Cardiomyocyte Proliferation by Promoting Cell Cycle Inhibitor mRNA Degradation

The authors identified Cnot3 as a critical regulator in cardiomyocyte proliferation at the late stage of cardiac differentiation from human embryonic stemcells. Cnot3 was highly expressed in cardiomyocytes with higher proliferation potential in both human and mouse, and its depletion resulted in a significant reduction in the proliferative capacity of cells. [Sci Rep] Full Article

TRIM24 Promotes while TRIM32 Inhibits Cardiomyocyte Hypertrophy via Regulation of Dysbindin Protein Levels

Researchers performed a yeast-two hybrid screen using dysbindin as bait against a cardiac cDNA library to identify the cardiac dysbindin interactome. Amongst several putative binding proteins, they identified tripartite motif-containing protein (TRIM) 24 and confirmed this interaction by co-immunoprecipitation and co-immunostaining. [J Biol Chem] Abstract | Full Article

Regulation of Histone Acetylation on Expression Profiles of Potassium Channels during Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells

Scientists investigated the expression pattern of the slow delayed rectifier potassium channel and the rapid delayed rectifier potassium channel using a model of mouse cardiomyocyte differentiation under different conditions of histone acetylation. They found that expression levels of both the delayed rectifier potassium channel and the inwardly rectifying potassium channel were more sensitive to histone hyperacetylation during differentiation from mouse embryonic stem cells into cardiomyocytes. [J Cell Biochem] Abstract

SKELETAL MUSCLE CELLS

Glucose Sensing by Skeletal Myocytes Couples Nutrient Signaling to Systemic Homeostasis

Investigators identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improved postprandial glucose disposal in mice, whereas its muscle-specific ablation impaired insulin action and led to postprandial glucose intolerance. [Mol Cell] Abstract | Graphical Abstract

Protectin DX Ameliorates Palmitate- or High-Fat Diet-Induced Insulin Resistance and Inflammation through an AMPK-PPARα-Dependent Pathway in Mice

The authors explored the effects of protectin DX (PDX) on hyperlipidemia-induced insulin resistance and inflammation through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα). PDX attenuated the impairment of insulin receptor substrate 1/Akt–mediated insulin signaling in palmitate-treated differentiated C2C12 cells and soleus skeletal muscle of high-fat diet-fed mice. [Sci Rep] Full Article

p38 MAPK Activation and H3K4 Trimethylation Is Decreased by Lactate In Vitro and High Intensity Resistance Training in Human Skeletal Muscle

Scientists investigated the effects of lactate (La) on p38 mitogen activated protein kinase (MAPK) and trimethylation of histone 3 lysine 4 (H3K4me3) in a model of activated satellite cells. They determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain leading to decreased differentiation of La-treated C2C12 cells after five days of repeated La treatment. [PLoS One] Full Article

SMOOTH MUSCLE CELLS

Loss of Smooth Muscle α-Actin Leads to NF-κB-Dependent Increased Sensitivity to Angiontensin II in Smooth Muscle Cells and Aortic Enlargement

The authors sought to identify the mechanism by which loss of smooth muscle isoform of α-actin causes aortic disease. Aortic tissue and explanted smooth muscle cells from Acta2^-/- aortas showed increased production of reactive oxygen radicals and increased basal NF-κB signaling, which lead to an increase in the expression of the angiotensin II (AngII) receptor type I and activation of signaling at 100-fold lower levels of AngII in the mutant compared to wild-type cells. [Circ Res] Abstract

Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling

Investigators determined the role and mechanism of Janus kinase 3 (JAK3) in vascular remodeling and smooth muscle cell (SMC) proliferation. Platelet-derived growth factor-BB, an SMC mitogen, induced JAK3 expression and phosphorylation while stimulating SMC proliferation. Janex-1, a specific inhibitor of JAK3, or knockdown of JAK3 by short hairpin RNA, inhibited the SMC proliferation. [Arterioscler Thromb Vasc Biol] Abstract

Moving Forward with the Neuromuscular Junction

The neuromuscular junction (NMJ) is indispensable for survival. This synapse between motoneurons and skeletal muscle fibers allows posture, movement and respiration. Therefore, its dysfunction creates pathologies than can be lethal. The molecular mechanisms of NMJ development and maintenance are the subject of intensive studies. The authors review some of the most recent discoveries. [J Neurochem] Abstract

Visit our reviews page to see a complete list of reviews in the muscle cell research field.

Audentes Therapeutics Announces Presentation of Data

Audentes Therapeutics, Inc. announced that data related to its product candidates AT132 for the treatment of X-linked Myotubular Myopathy, and AT342 for the treatment of Crigler Najjar Syndrome, will be presented. [Press release from Audentes Therapeutics, Inc. discussing research to be presented at the 20^th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), Washington, D.C.] Press Release

ALS Association Applauds FDA for Speedy Approval of New ALS Drug

The ALS Association applauded the Food and Drug Administration’s (FDA’s) announcement that it has approved Radicava, the first new treatment approved specifically for ALS in 22 years. The FDA approved Radicava less than a year after Mitsubishi Tanabe Pharma Corporation submitted a New Drug Application. [The ALS Association] Press Release

GW Researcher Receives $1.7 Million Federal Grant to Continue Study of the Hedgehog Receptor

Xiaoyen Zheng, Ph.D., assistant professor of anatomy and regenerative biology at the George Washington (GW) University School of Medicine and Health Sciences, who recently received a $1.7 million grant from the National Institutes of Health and National Institute of General Medical Sciences, is determined to learn more about the Hedgehog pathway. [The George Washington University] Press Release

Scientists Relieved by Emmanuel Macron’s French Election Victory

French scientists say they’re relieved and happy that their country’s next president will be Emmanuel Macron, a 39-year-old former civil servant and economy minister who swept to victory in elections. Macron intends to make cuts to public spending, but has said he will ring-fence the budgets for research and higher education, areas that he wants to make the central plank of a program to boost innovation and cut unemployment. [Nature News] Editorial

Money Still Missing as the Plan to Synthesize a Human Genome Takes Another Step Forward

More than 200 biologists, businesspeople, and ethicists will converge upon the New York Genome Center in Manhattan to jumpstart what they hope will be biology’s next blockbuster: Genome Project-write, a still-unfunded sequel to the Human Genome Project where instead of reading a human genome, scientists create one from scratch and incorporate it into cells for various research and medical purposes. [ScienceInsider] Editorial

French Plan to Create €5-Billion Science ‘Super-Campus’ in Disarray

French ambitions to create a €5-billion (US$5.5-billion) science ‘super-campus’ near Paris by 2020 seem to be in falling further apart, after a compromise scheme to save the troubled project was rejected by one of its creators. [Nature News] Editorial

NIH Grant Limits Rile Biomedical Research Community

A decision by the US National Institutes of Health (NIH) to limit its grant support for individual researchers has sparked concerns that the policy could discourage collaboration or divert funding from the best science. The move has alarmed some researchers who agree with the NIH’s stated aim of freeing up money for young scientists, who often struggle to obtain research grants. [Nature News] Editorial

NEW Gordon Research Conferences: Cancer Nanotechnology
June 18-23, 2017
West Dover, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Associate – Genetics of Muscular Dystrophy (University of Florida College of Medicine)

Postdoctoral/ Graduate Student Positions – Neuromuscular Diseases (University of Alberta)

PhD Studentship – Experimental Genetic Cardiology (Oslo University Hospital)

Postdoctoral Position(s) – Skeletal and Cardiac Muscle Disease Modeling and Regeneration (Duke University)

PhD Student – Molecular Cardiology (University Medical Center Schleswig-Holstein)

Research Fellow – Cardiovascular Science (Columbia University)

International PhD Program – Biomedical Research (Institute of Genetics & Molecular & Cellular Biology/CERBM GIE)

Principal Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

Postdoctoral Fellow – Cardiovascular Disease (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Vascular Smooth Muscle (The University of Tennessee Health Science Center)

Postdoctoral Fellow – Skeletal Muscle (University of Oregon)

Postdoctoral Fellowship – Heart Regeneration (Children’s Hospital Los Angeles – University of Southern California)

Postdoctoral Fellow – Epigenomics of Cardiac Development and iPSC/ESC Differentiation (Stanford Cardiovascular Institute)

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