Muscle Cell News Volume 4.20 | Jun 10 2019

TOP STORY

iPSC-Derived Cardiomyocytes Reveal Aberrant ERK5 and MEK1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome

Researchers used patient-derived RAF1^S257L/+ and CRISPR-Cas9-generated isogenic control induced pluripotent stem cell (iPSC)-derived cardiomyocytes to model noonan syndrome RAF1-associated hypertrophic cardiomyopathy and to further delineate the molecular mechanisms underlying the disease. [Circulation] Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

MicroRNA-221 Is Cardioprotective and Anti-Fibrotic in a Rat Model of Myocardial Infarction

Using in vitro hypoxia/reperfusion (H/R) of H9c2 and rat cardiac fibroblast (cFB) models, miR-221 protected H9c2 through combined anti-apoptotic and anti-autophagic effects and cFB via anti-autophagic effects alone in H/R. It inhibited myofibroblast activation as indicated by lowering α-SMA expression, gel contraction and collagen synthesis. [Mol Ther Nucleic Acids] Abstract | Graphical Abstract

c-Kit Haploinsufficiency Impairs Adult Cardiac Stem Cell Growth, Myogenicity and Myocardial Regeneration

Cardiomyocyte formation was measured with different doses and duration of BrdU or EdU. The authors compared the myogenic and regenerative potential of the c-kit^Cre cardiac progenitor cells (CSCs) with wild type CSCs. [Cell Death Dis] Full Article

The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing

The re-entry formation, conduction velocity, and maximum capture rate were investigated in a monolayer of human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a healthy donor and in a neonatal rat ventricular myocyte monolayer using the optical mapping method under erythromycin concentrations of 15, 30, and 45 μM. [Cardiovasc Toxicol] Abstract

miR-27 Alleviates Myocardial Cell Damage Induced by Hypoxia/Reoxygenation via Targeting TGFBR1 and Inhibiting NF-κB Pathway

H9c2 cells were transfected with miR-27 mimic/inhibitor. Then the cell proliferation was tested by MTT assay and the cell apoptosis was detected by flow cytometry. The luciferase activity assay was utilized to analyze the relationship between miR-27 and TGFBR1. [Kaohsiung J Med Sci] Full Article

SKELETAL MUSCLE CELLS

Genome Editing of Expanded CTG Repeats within the Human DMPK Gene Reduces Nuclear RNA Foci in Muscle of DM1 Mice

Co-expression of Staphylococcus aureus (Sa)Cas9 and selected pairs of single guide RNAs in cultured myotonic dystrophy type 1 (DM1) patient-derived muscle line cells carrying 2600 CTG resulted in targeted DNA deletion, ribonucleoprotein foci disappearance and correction of splicing abnormalities in various transcripts. Furthermore, a single intramuscular injection of recombinant AAV vectors expressing CRISPR-SaCas9 components in tibialis anterior muscle of DMSXL mice decreased the number of pathological RNA foci in myonuclei. [Mol Ther] Abstract

Cytoplasmic Sequestration of the RhoA Effector mDiaphanous1 by Prohibitin2 Promotes Muscle Differentiation

Scientists report that mDiaphanous1, an effector of adhesion-dependent RhoA-signaling, negatively regulated myogenesis at the level of Myogenin expression. In myotubes, over-expression of mDia1ΔN3, a RhoA-independent mutant, suppressed Myogenin promoter activity and expression. [Sci Rep] Full Article

Skeletal Muscle Differentiation Drives a Dramatic Downregulation of RNA Polymerase III Activity and Differential Expression of Polr3g Isoforms

Investigators describe the differential expression of polymerase (Pol)r3g and its alternate isoform Polr3gL during embryonic development and using a custom tRNA microarray, they demonstrated their distinct activity on the synthesis of tRNA isoacceptors. They showed that Pol III dependent transcripts were dramatically down-regulated during the differentiation of skeletal muscle, as were mRNAs coding for Pol III associated proteins Brf1 and Brf2, while Polr3gL was up-regulated alongside contractile protein genes. [Dev Biol] Abstract

SMOOTH MUSCLE CELLS

Inhibition of Polycomb Repressor Complex 2 Ameliorates Neointimal Hyperplasia by Suppressing Trimethylation of H3K27 in Vascular Smooth Muscle Cells

Human aortic vascular smooth muscle cells were challenged with platelet-derived growth factor-BB and total histones were extracted and analyzed by HPLC/MS. For the in vivo study, rats were subjected to wire-guided common carotid injury. [Br J Pharmacol] Abstract

Smooth Muscle Cell-Specific TMEM16A Deletion Does Not Alter Ca²⁺ Signaling, Uterine Contraction, Gestation Length or Litter Size in Mice

Scientists employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. They found that myometrial cells from TMEM16ASMKO mice generated the same pattern and magnitude in Ca²⁺ signals upon stimulation with KCl, oxytocin and PGF2α compared to isogenic control myometrial cells. [Biol Reprod] Abstract

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The Role of GDF11 in Aging and Skeletal Muscle, Cardiac and Bone Homeostasis

There have been several studies examining the effect of GDF11 and/or the downstream ActRII pathway on cardiac function, along with several interesting reports on bone. The authors present a review of the GDF11 literature, as it relates in particular to aging and skeletal muscle, cardiac and bone biology. [Crit Rev Biochem Mol Biol] Abstract

The Role of the Microcirculation in Muscle Function and Plasticity

The investigators discuss the role that skeletal muscle microcirculation plays in muscle function and plasticity. Besides the density of the capillary network, also the distribution of capillaries is crucial for adequate muscle oxygenation. [J Muscle Res Cell Motil] Full Article

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

Applied Therapeutics to Present Data Highlighting AT-001 for the Treatment of Diabetic Cardiomyopathy

Applied Therapeutics, Inc. announced that it will present data on AT-001, a novel, potent and selective aldose reductase inhibitor in clinical development for diabetic cardiomyopathy (DbCM). The poster, entitled “Phase I/II Safety and Proof of Biological Activity Study of AT-001, an Aldose Reductase Inhibitor in Development for Diabetic Cardiomyopathy” highlights a recently completed Phase I/II study in approximately 120 patients with type 2 diabetes, a subset of which had DbCM. [Press release from Applied Therapeutics Inc. discussing research presented at the American Diabetes Association 79^th Scientific Sessions, San Fransico] Press Release

Scholar Rock Announces Positive Final Results from Phase I Clinical Trial of SRK-015 in Healthy Volunteers

Scholar Rock Holding Corporation announced positive final top-line results from the Phase I clinical trial of its product candidate, SRK-015, a highly specific inhibitor of myostatin activation, in healthy adult volunteers. Consistent with previously announced interim findings, the final results showed robust and sustained target engagement and no apparent safety signals were observed across all tested doses. [Press release from Scholar Rock Holding Corporation discussing research to be presented at the Cure SMA Annual Conference, Anaheim] Press Release

Heart Patches Set for Human Trials

Researchers have shown that heart ‘patches’ grown in the lab are safe to move on to trials in people with hearts damaged after a heart attack. These patches could one day cure debilitating heart failure, which affects an estimated 920,000 people in the UK and is on the rise as more and more people survive a heart attack. [Press release from The British Heart Foundation discussing research presented at the the British Cardiovascular Society (BCS) Conference, Manchester] Press Release

Vertex Expands into New Disease Areas and Enhances Gene Editing Capabilities through Expanded Collaboration with CRISPR Therapeutics and Acquisition of Exonics Therapeutics

Vertex Pharmaceuticals Incorporated announced that the company is enhancing its gene editing capabilities to develop novel therapies for Duchenne Muscular Dystrophy and Myotonic Dystrophy Type 1 by expanding its collaboration with CRISPR Therapeutics and acquiring Exonics Therapeutics. [Vertex Pharmaceuticals Incorporated] Press Release

Quantum Genomics Enrolls First Patient in QUORUM Phase IIb Study of Firibastat in Heart Failure Patients

Quantum Genomics announced the enrollment of the first patient in its QUORUM Phase IIb study of lead clinical candidate, firibastat, in patients with heart failure after acute myocardial infarction. Firibastat is a first-in-class brain aminopeptidase A inhibitor, being developed for the treatment of resistant hypertension and heart failure. [Quantum Genomics] Press Release

Judge Says FDA Can Stop Clinic from Selling Stem Cell Treatments

The decision may facilitate the agency cracking down more effectively on the unproven interventions these companies sell. [The Scientist] Editorial

Powerful US Senator Calls for Vetting NIH Grantees at Hearing on Foreign Influences

Research typically enjoys bipartisan support in the US Congress. But when it comes to the increasingly contentious topic of academic espionage by foreign governments, politics is never far from the surface. At a hearing of the Senate Committee on Finance, Chairman Chuck Grassley urged federal agencies to do more to thwart “real, aggressive, and ongoing” attempts by foreign entities to steal the fruits of US-funded research. [ScienceInsider] Editorial

Hungarians Protest against Proposed Government Takeover of Science

Thousands of scientists and their supporters marched through the streets of Budapest on 2 June to protest against a proposed law that would give the Hungarian government direct control of the country’s top research institutes. [Nature News] Editorial

NEW International Conference on Muscle Wasting
September 23-28, 2019
Ascona, Switzerland

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

NEW Postdoctoral Researchers – Cardiovascular Studies (Virginia Tech)

Postdoctoral – Proteomics of Muscles and Aging (Oklahoma Medical Research Foundation)

Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

Postdoctoral Fellow – Cardiac and Skeletal Muscle Engineering (Georgia Institute of Technology & Emory University School of Medicine)

Postdoctoral Fellow – Muscular Growth, Wasting, and Dystrophy (University of Louisville)

Postdoctoral Fellow – Cardiovascular Epidemiology (Boston University School of Medicine)

Postdoctoral Fellow – Molecular Cardiology (University of Illinois at Chicago)

Senior Research Investigator – Multiple Sclerosis Research (Thomas Jefferson University)

Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California, Davis)

Assistant Specialist – Cardiovascular Research (University of California, Davis)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (University of California, Davis)

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