Muscle Cell News Volume 4.40 | Dec 2 2019

TOP STORY

Smooth Muscle Cell-Specific Fibronectin-EDA Mediates Phenotypic Switching and Neointimal Hyperplasia

Using human coronary artery sections with a bare metal stent, researchers demonstrated the expression of fibronectin-splice variant containing extra domain (Fn-EDA) in the vicinity of smooth muscle cells (SMC)-rich neointima and peri-strut areas. In mice, Fn-EDA co-localized with SMCs in the neointima of injured carotid arteries and promoted neointima formation in the co-morbid condition of hyperlipidemia by potentiating SMC proliferation and migration. [J Clin Invest] Full Article | Graphical Abstract

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CARDIAC MUSCLE CELLS

Resolving Titin’s Lifecycle and the Spatial Organization of Protein Turnover in Mouse Cardiomyocytes

The authors found titin mRNA, protein synthesis and degradation compartmentalized toward the Z-disk in adult, but not embryonic cardiomyocytes. Originating at the Z-disk, titin contributed to a soluble protein pool before it is integrated into the sarcomere lattice. Titin integration, disintegration, and reintegration were stochastic and did not proceed sequentially from Z-disk to M-band, as suggested previously. [Proc Natl Acad Sci USA] Abstract

TGF-β Signaling Promotes Tissue Formation During Cardiac Valve Regeneration in Adult Zebrafish

Investigators used adult zebrafish and found that, upon valve decellularization, they initiated a rapid regenerative program that leads to the formation of new functional valves. After injury, endothelial and kidney marrow-derived cells underwent cell cycle re-entry and differentiated into new extracellular matrix-secreting valve cells. [Dev Cell] Full Article | Graphical Abstract

ERK1/2 Phosphorylation of FHOD Connects Signaling and Nuclear Positioning Alternations in Cardiac Laminopathy

The authors showed that cardiomyocytes from mice with a lamin A/C gene mutation and elevated cardiac ERK1/2 activity have altered nuclear positioning. In fibroblasts, ERK1/2 activation negatively regulated nuclear movement by phosphorylating S498 of FHOD1. Expression of an unphosphorylatable FHOD1 variant rescued the nuclear movement defect in fibroblasts expressing a cardiomyopathy-causing lamin A mutant. [Dev Cell] Abstract | Graphical Abstract

PRMT1 Suppresses ATF4-Mediated Endoplasmic Reticulum Response in Cardiomyocytes

Scientists demonstrated a critical role for PRMT1 in the control of endoplasmic reticulum (ER) stress in cardiomyocytes. The inhibition of PRMT1 augmented tunicamycin-triggered ER stress response in cardiomyocytes while PRMT1 overexpression attenuates it. [Cell Death Dis] Full Article

The Long Non-Coding RNA TUG1-miR-9a-5p Axis Contributes to Ischemic Injuries by Promoting Cardiomyocyte Apoptosis via Targeting KLF5

Researchers showed the interplay between long non-coding RNA taurine-upregulated gene 1 (lncR-TUG1), miR-9a-5p and Krüppel-like factor 5 (KLF5). LncR-TUG1 was upregulated in ischemic heart and in cultured cardiomyocytes exposed to H₂O₂. Knockdown of lncR-TUG1 markedly ameliorated impaired cardiac function of myocardial infraction mice. [Cell Death Dis] Full Article

Plk2 Regulated by miR-128 Induces Ischemia Reperfusion Injury in Cardiac Cells

Investigators demonstrated that ischemia-reperfusion injury upregulated the expression of Plk2 but decreases miR-128 expression in heart cells both in vitro and in vivo. Silencing Plk2 using siRNA protected cells from Antimycin A induced cell apoptosis/death. Silencing Plk2 also decreased phosphorylated p65 expression but increased Angiopoietin 1 expression. [Mol Ther Nucleic Acids] Abstract | Full Article

Integrin Alpha-5 Subunit Is Critical for the Early Stages of Human Pluripotent Stem Cell Cardiac Differentiation

Scientists performed a profile of integrin expression in two stages of cardiac differentiation: mesodermal progenitors and cardiomyocytes. They found an active regulation of the expression of different integrins during cardiac differentiation. [Sci Rep] Full Article

SKELETAL MUSCLE CELLS

Endothelial EphB4 Maintains Vascular Integrity and Transport Function in Adult Heart

The authors showed that inducible and endothelial cell-specific inactivation of Ephb4 in adult mice was compatible with survival, but led to rupturing of cardiac capillaries, cardiomyocyte hypertrophy, and pathological cardiac remodeling. In contrast, EphB4 was not required for integrity and homeostasis of capillaries in skeletal muscle. [eLife] Full Article

DEL-1 Ameliorates High-Fat Diet-Induced Insulin Resistance in Mouse Skeletal Muscle Through SIRT1/SERCA2-Mediated ER Stress Suppression

Developmental endothelial locus-1 (DEL-1) treatment augmented SIRT1 expression in C2C12 myocytes, thereby increasing SERCA2 expression in a dose-dependent fashion, and attenuated endoplasmic reticulum (ER) stress and insulin resistance under palmitate treatment condition. SIRT1/SERCA2 knockdown abrogated effects of DEL-1 on palmitate-induced insulin resistance as well as ER stress. [Biochem Pharmacol] Abstract | Graphical Abstract

6-Bromoindirubin-3′-Oxime Intercepts GSK3 Signaling to Promote and Enhance Skeletal Muscle Differentiation Affecting miR-206 Expression in Mice

Using C2C12 cells, researchers examined 6-bromoindirubin-3′-oxime’s (BIO’s) effect during myoblast proliferation and differentiation showing that BIO treatment promoted transition from cell proliferation to myogenic differentiation through the arrest of cell cycle. They showed that BIO was able to promote myogenic differentiation in damaged myotubes in vitro by enriching the population of newly formed skeletal muscle myotubes. [Sci Rep] Full Article

SMOOTH MUSCLE CELLS

Mini Tryptophanyl-tRNA Synthetase Is Required for a Synthetic Phenotype in Vascular Smooth Muscle Cells Induced by IFN-γ-Mediated β2-Adrenoceptor Signaling

Researchers provide evidence to support an essential dependency of interferon gamma (IFN-γ)-induced activation and synthetic phenotype in vascular smooth muscle cells (AoSMC) on mini-TrpRS. This was based upon change in AoSMC morphology from epithelioid to spindle-shaped cells and expression of proteins and genes important in mediating or regulating contractile function of AoSMC, following blockade of mini-TrpRS induced by IFN-γ, via targeted siRNA or the decoy cognate amino acid D-Tryptophan. [Cytokine] Abstract | Graphical Abstract

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Evasion of Apoptosis by Myofibroblasts: A Hallmark of Fibrotic Diseases

Myofibroblasts are scar-forming cells that are ultimately responsible for the excessive synthesis, deposition and remodeling of extracellular matrix proteins in fibrosis. Advances have been made in biology’s understanding of the mechanisms that keep myofibroblasts in an activated state and control myofibroblast functions. However, the mechanisms that help myofibroblasts to persist in fibrotic tissues remain poorly understood. [Nat Rev Rheumatol] Abstract

Mixing It Up: The Biological Significance of Hybrid Skeletal Muscle Fibers

Although hybrid fibers have been recognized by muscle biologists for more than three decades, uncertainty persists about their prevalence in normal muscles, their role in fiber-type transitions, and what they might tell us about fiber-type regulation at the cellular and molecular levels. The author summarizes current knowledge on the relative abundance of hybrid fibers in a variety of muscles from different species. [J Exp Biol] Abstract

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Novoheart to Co-Develop First of Its Kind Human Heart-in-a-Jar Model of Heart Failure With AstraZeneca

Novoheart announced a collaboration with AstraZeneca, in an effort to develop the world’s first human-specific in vitro, functional model of heart failure with preserved ejection fraction, a common condition especially among the elderly and in women, with the reported prevalence approaching 10% in women over the age of 80 years. [Novoheart Holdings, Inc.] Press Release

CARMAT Granted Authorization to Resume the PIVOTAL Study in Kazakhstan

CARMAT announced that it has received authorization to resume the PIVOTAL study on artificial hearts in Kazakhstan. [CARMAT] Press Release

ARCS Foundation Awards $225,000 in Fellowships to UC San Diego Graduate Students

The Achievement Rewards for College Scientists (ARCS) Foundation has awarded a total of $225,000 to 30 graduate students at the University of California (UC) San Diego for the 2019-20 academic year. The annual fellowship awards recognize exceptional students in the natural sciences, engineering and medicine. [University of California San Diego] Press Release

Elsevier Progresses in Open-Access Deal Making

The scholarly publisher has announced several new licensing agreements in both Europe and the US, but some major academic groups are still without contracts and access to journals. [The Scientist] Editorial

Chinese Ministry Investigates Duplications in Papers by University President

The Chinese education ministry is investigating scientific articles authored by high-profile immunologist and university president Cao Xuetao, following suggestions that dozens of papers contain potentially problematic images. Four journals also say they are examining papers from Cao. [Nature News] Editorial

NEW Beyond a Million Genomes: From Discovery to Precision Health
January 21-25, 2020
Breckenridge Colorado, United States

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NEW Postdoctoral Researcher – Skeletal Muscle Aging (St. Jude Children’s Research Hospital)

NEW Senior Scientist – Muscle Cell Biology (Shape Therapeutics)

Asistant Professor – Ion Channels (University of Tennessee)

Assistant Professor – Muscle Biology (Purdue University)

Postdoctoral Researcher – Larngeal Muscle Development (Columbia University)

Postdoctoral Researcher – Genome Editing in Cardiac Microtissues (The Jackson Laboratory)

Research Scientists – Cardiac and Neuronal Cell Differentiation (Evotec)

Research Scientist – Metabolic & Muscle Diseases (Regeneron)

Research Scientist – Gene Therapy for Neuromuscular Disorders (Vertex Pharmaceuticals)

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

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