Extracellular Matrix News Volume 10.05 | Feb 14 2019

TOP STORY

MicroRNA-Dependent Regulation of Biomechanical Genes Establishes Tissue Stiffness Homeostasis

Inhibition of DROSHA or argonaute 2, or disruption of microRNA recognition elements within individual target mRNAs, such as connective tissue growth factor, induced hyper-adhesive, hyper-contractile phenotypes in endothelial and fibroblast cells in vitro, and increased tissue stiffness, contractility and ECM deposition in the zebrafish fin fold in vivo. [Nat Cell Biol] Abstract | Press Release

(Ranked by impact factor of the journal)

Non-Immune Cell-Derived ICOS Ligand Functions as a Renoprotective αvβ3 Integrin-Selective Antagonist

The authors report a novel, renoprotective role for inducible costimulator (ICOS) ligand (ICOSL) in early kidney disease through its selective binding to podocyte αvβ3 integrin. Contrary to ICOSL’s immune-regulatory role, ICOSL in non-hematopoietic cells limited the activation of αvβ3 integrin. [J Clin Invest] Abstract | Full Article

Gα_s-Coupled Receptor Signaling and Sleep Regulate Integrin Activation of Human Antigen-Specific T Cells

Using multimers of peptide major histocompatibility complex molecules and of ICAM-1-the ligand of β2-integrins- researchers showed that the Gα_s-coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2, PGD2, and adenosine strongly inhibited integrin activation on human CMV- and EBV-specific CD8⁺ T cells in a dose-dependent manner. [J Exp Med] Full Article | Graphical Abstract

Dynamically Stiffened Matrix Promotes Malignant Transformation of Mammary Epithelial Cells via Collective Mechanical Signaling

Mammary epithelial cells formed and remained as spheroids, but began to lose epithelial characteristics and gain mesenchymal morphology upon matrix stiffening. However, both the degree of matrix stiffening and culture time before stiffening played important roles in regulating this conversion as, in both cases, a subset of mammary spheroids remained insensitive to local matrix stiffness. [Proc Natl Acad Sci USA] Abstract | Press Release

Tumor Cell Blebbing and Extracellular Vesicle Shedding: Key Role of Matrikines and Ribosomal Protein SA

Investigators demonstrated that ECM degradation products like elastin degradation products induced tumor amoeboid phenotype with cell membrane blebbing and shedding of extracellular vesicle containing Hsp90 and proteinases in the extracellular space. [Br J Cancer] Abstract

Cardiac Fibroblast Activation and Hyaluronan Synthesis in Response to Hyperglycemia and Diet-Induced Insulin Resistance

Scientists report that cardiac fibroblasts isolated from mice on a diabetogenic diet acquired pro-fibrotic gene expression without a concomitant increase in hyaluronan (HA) matrix deposition. Additionally, hyperglycemia alone did not stimulate HA synthesis or cardiac fibroblast activation in vitro, suggesting that the direct effect of hyperglycemia on fibroblasts was not the primary driver of fibrotic remodeling in cardiac diabetic maladaptation. [Sci Rep] Full Article

Human Trophoblast Requires Galectin-3 for Cell Migration and Invasion

Silencing of galectin-3 induced significant reduction in cell migration and invasion, which was restored by rhgalectin-3. The influence on known mediators of cell invasion, MMP2 and -9, and integrins α1, α5, and β1 was followed in silenced cells, showing lower levels of MMPs and a large reduction in integrin subunit β1. [Sci Rep] Full Article

Sustained Release of N-Acetylcysteine by Sandwich Structured Polycaprolactone/Collagen Scaffolds for Wound Healing

Investigators prepared a sandwich structured poly-caprolactone (PCL)-Col/N-acetylcysteine (NAC) scaffold using the molding method, which consisted of PCL nanofibers at the core and NAC-loaded collagen on both sides. PCL-Col/NAC scaffolds presented better properties than the control groups in cell migration and proliferation. [J Biomed Mater Res A] Abstract

BMP9 Promotes the Extracellular Matrix of Nucleus Pulposus Cells via Inhibition of the Notch Signaling Pathway

Researchers found that BMP9 promoted the expression of ECM in nucleus pulposus cells (NPCs), and the key molecules of Notch signaling, namely, NICD-1, hes and hey, were significantly altered in BMP9-transfected NPCs, which suggests that BMP9 may regulate the ECM via the Notch signaling pathway. [DNA Cell Biol] Abstract

Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3

Alpha-granule secretion increased in mice lacking RhoBTB3 in response to thrombin, collagen related peptide and U46619/ADP. Integrin activation and spreading on fibrinogen and collagen under static conditions were also unimpaired; however, scientists observed reduced platelet accrual on collagen under flow conditions. [Cells] Full Article

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The Blood-Brain Barrier and Beyond: Nano Based Neuropharmacology and the Role of Extracellular Matrix

The authors outline the state-of-the art knowledge on blood-brain barrier passage, address the significant influence of pathological conditions on nanoparticulate drug delivery, and highlight the largely neglected role of the ECM. [Nanomedicine] Abstract | Graphical Abstract

Extracellular Matrix-Mediated Regulation of Cancer Stem Cells and Chemoresistance

Investigators outline parallels between development, wound repair and cancer to discuss how changes in ECM dynamics influence stem cell function during normal physiological processes and pathological states, as well as the transition between the two in the form of precancerous lesions. [Int J Biochem Cell Biol] Abstract

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

Forbius Announces a Clinical Trial Collaboration with the Myeloproliferative Neoplasm Research Consortium to Evaluate AVID200, a Novel TGF-Beta Inhibitor, in Myelofibrosis

Forbius announced a collaboration agreement with the Icahn School of Medicine at Mount Sinai and the Myeloproliferative Neoplasm Research Consortium. This collaboration will launch an investigator-initiated trial evaluating AVID200, a highly potent and isoform-selective TGF-beta inhibitor, as a potential treatment for myelofibrosis. [Forbius] Press Release

Ortho RTi Announces Initiation of Pivotal Study on Ortho-R for Rotator Cuff Repair

Ortho Regenerative Technologies Inc. announced the initiation of a six-month pivotal animal study on Ortho-R for rotator cuff repair. In addition, a pre-Investigational New Drug meeting is to be held with the FDA to formalize the requirements for the filing of its application to commence human trials on Ortho-R. [Ortho Regenerative Technologies Inc.] Press Release

Genkyotex Announces Award of Grant from Cancer Research UK to Academic Partner to Further Develop NOX Research in Oncology

Genkyotex announced that Professor Gareth Thomas of the University of Southampton was awarded a Biotherapeutics Drug Discovery Project grant by Cancer Research UK to conduct a research program focused on the role of NOX inhibition in oncology. [Genkyotex] Press Release

SpinalCyte Announces New Canadian Patent

SpinalCyte, LLC announced the issuance of a new patent in Canada. The patent adds to the company’s intellectual property portfolio with 37 US and international patents issued with 100+ patents pending focused on fibroblast technologies. [SpinalCyte, LLC (PR Newswire Association LLC.)] Press Release

NYU Tandon Professor Named to Elite AAAS Fellowship

The American Association for the Advancement of Science (AAAS) named Jin Kim Montclare, a professor in the Department of Chemical and Biomolecular Engineering at the NYU Tandon School of Engineering, a 2019-20 AAAS Leshner Public Engagement Fellow. The Montclare Lab for Protein Engineering and Molecular Design has been responsible for several biomaterials, biocatalytic, and therapeutic research breakthroughs in recent years. [NYU Tandon School of Engineering] Press Release

US Science Agencies Set for Budget Boost in Deal to Avert Government Shutdown

With less than two days to go before the US government runs out of money, lawmakers in Congress are scrambling to pass a budget deal that would give small increases to NASA, the National Science Foundation, the Environmental Protection Agency and many other science agencies. [Nature News] Editorial

Hungarian Researchers Protest against Government Changes to Funding

Thousands of scientists took to the streets in Hungary to protest changes to government research funding. The demonstrations, which saw people hold books above their heads and form a human chain around Budapest’s Academy of Sciences building, are just the latest in a series of clashes between researchers and the country’s populist government over academic freedom. [The Scientist] Editorial

Draft Federal Spending Deal Includes Largest Boost for FDA in Five Years

A government funding deal released includes $269 million in new funding for the FDA, which would represent the largest increase the agency has seen in at least five years. With that new funding, the FDA would receive $3.08 billion in government funding for fiscal year 2019. Coupled with roughly $2.5 billion in fees from drug, device, and other regulated companies, FDA’s total budget would be $5.67 billion. [STAT News] Editorial

NEW Gordon Research Conference: Metalloproteases
May 12-17, 2019
Lucca, Italy

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

NEW Tenure Track Professor Position – Architectured Biomedical Materials for Tissue Regeneration (Charite Universitatsmedizin Berlin)

Scientist – Matrix Biology (STEMCELL Technologies Inc.)

Postdoctoral Scholar – Computational Modeling of Cell-Matrix Interactions (Washington University, St. Louis)

Assistant Professor – Development & Re-Generation of Biological Systems (ETH Zurich)

Research Associate – Microstructure Core Facility Leader (TU Dresden)

Tenure Track Associate Professor – Molecular Cell Biology (Aarhus University)

Tenure Track Assistant Professor – Regenerative Medicine (University of British Columbia)

Associate Senior Lecturer – Molecular Medicine/Regenerative Medicine (Lund University)

Postdoctoral Associate – Planar Cell Polarity (Stony Brook University)

Postdoctoral Fellowship – Tissue Fibrosis Resolution (UCSF Cardiovascular Research Institute)

Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine)

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