Extracellular Matrix News Volume 8.25 | Jun 29 2017

TOP STORY

Designed Proteins to Treat Muscular Dystrophy

The cell scaffolding holds muscle fibers together and protects them from damage. Individuals who suffer from muscular dystrophy often lack essential components in this cell scaffold. Scientists have now designed two proteins that stabilize the cell scaffolding and link it to the muscle fiber, thereby restoring muscle structure and function. [Press release from the University of Basel discussing online prepublication in Science Translational Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Quantitative Proteomics Identify Tenascin-C as a Promoter of Lung Cancer Progression and Contributor to a Signature Prognostic of Patient Survival

To investigate the contribution of the microenvironment to lung fibrosis and adenocarcinoma progression, researchers used mouse models to characterize the ECM composition of normal lung, fibrotic lung, lung tumors, and metastases. Using quantitative proteomics, they identified and assayed the abundance of 113 ECM proteins, which revealed robust ECM protein signatures unique to fibrosis, primary tumors, or metastases. [Proc Natl Acad Sci USA] Abstract

Organ Sculpting by Patterned Extracellular Matrix Stiffness

Investigators showed that organs can be sculpted instead by patterning anisotropic resistance within their ECM. Using direct biophysical measurements of elongating Drosophila egg chambers, they documented robust mechanical anisotropy in the ECM-based basement membrane but not the underlying epithelium. [eLife] Abstract | Full Article (Download)

Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors

Researchers describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors of MMP-13. Their compounds exhibited at least 500-fold selectivity versus other MMPs. [J Med Chem] Abstract | Graphical Abstract

IL-1β Increases Asporin Expression via the NF-κB p65 Pathway in Nucleus Pulposus Cells during Intervertebral Disc Degeneration

Asporin is an ECM protein that has been shown to be increased in degenerated intervertebral discs, but little is known about how asporin is regulated during disc degeneration. Scientists confirmed that asporin was abundantly increased in patients’ degenerated nucleus pulposus. Mechanistically, IL-1β upregulated asporin expression by activating the p65 pathway in human nucleus pulposus cells. [Sci Rep] Full Article

Cellular Uptake of proMMP-2:TIMP-2 Complexes by the Endocytic Receptor Megalin/LRP-2

Investigators showed that, in BN16 rat yolk sac cells, the zymogen form of MMP-2 (proMMP-2):TIMP-2 complex was endocytosed through a distinct lipoprotein receptor-related protein (LRP) member, megalin/LRP-2. Addition of receptor-associated protein, a natural LRP antagonist, caused accumulation of endogenous proMMP-2 and TIMP-2 in conditioned media. [Sci Rep] Full Article

Monocyte Adhesion, Migration, and Extracellular Matrix Breakdown Is Regulated by Integrin αVβ3 in Mycobacterium tuberculosis Infection

In a cohort of tuberculosis patients, scientists detected significantly increased integrin β3 mRNA accumulation in induced sputum compared with control subjects. Integrin αVβ3 colocalized with areas of increased and functionally active MMP-1 on infected monocytes, and αVβ3 blockade markedly decreased type I collagen breakdown, and impaired both monocyte adhesion and leukocyte migration in a transwell system. [J Immunol] Abstract | Full Article

Post-Translational Modification of the Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Cytoplasmic Tail Impacts Ovarian Cancer Multicellular Aggregate Dynamics

To investigate the potential role of membrane type 1 (MT1)-MMP cytoplasmic residue Thr567 phosphorylation in regulation of metastasis-associated behaviors, researchers engineered ovarian cancer cells that expressed low endogenous levels of MT1-MMP to express wild-type MT1-MMP, a phospho-mimetic mutant or a phospho-deficient mutant. Their results showed that Thr567 modulation influenced behavior of both individual cells and multi-cellular aggregates. [J Biol Chem] Abstract | Full Article

Mapping the Recognition Domains of Pneumococcal Fibronectin-Binding Proteins PavA and PavB Demonstrates a Common Pattern of Molecular Interactions with Fibronectin Type III Repeats

The authors deciphered the molecular interaction between fibronectin and Streptococcus pneumoniae (pneumococcal) fibronectin-binding proteins (FnBPs) PavA and PavB, respectively. They showed in adherence and binding studies that the pneumococcal interaction with fibronectin is a non-human specific trait. Both pneumococcal FnBPs recognized similar peptides in targeted type III repeats. [Mol Microbiol] Abstract

The Effect of Collagen Coating on Titanium with Nanotopography on In Vitro Osteogenesis

Scientists hypothesized that the association of nanotopography with collagen may increase the in vitro osteogenesis on a Ti surface. Surface characterization evidenced that collagen coating did not alter the nanotopography. Collagen coating increased cell proliferation, alkaline phosphatase activity, extracellular matrix mineralization and collagen type 1a, OSX, osteocalcin and Bcl2 associated X protein gene expression. [J Biomed Mater Res A] Abstract

Mechanistic Understanding of Nanoparticles’ Interactions with Extracellular Matrix: The Cell and Immune System

The authors critically discuss the specific behavior of nanoparticles (NPs) that are within the ECM domain and passing through the biological barriers. Regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions [Part Fibre Toxicol] Full Article

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

Carmell Therapeutics Announced the Issuance of Canadian Patent No. 2701187 for Methods and Apparatus for Manufacturing Plasma Based Plastics

Carmell Therapeutics will soon be conducting a Phase III clinical study for its first product/indication, Bone Healing Accelerant. The plasma-based bioactive material technology was developed at Carnegie Mellon University and utilizes pooled plasma to create products which accelerate the healing of both bone and soft tissues. [Carmell Therapeutics] Press Release

UTSA Student Start-Up Helps Breast Cancer Survivors Regenerate Nipples

UTSA graduate students are winning pitch competitions left and right with their new start-up, NovoThelium, which uses bioengineered scaffolds to allow women to regenerate a nipple after a mastectomy. [The University of Texas at San Antonio] Press Release

Cholera Vaccine Faces Major Test in War-Torn Yemen

Public health experts and international groups are fighting an explosive cholera outbreak in Yemen. A group managing the modest global reserve of cholera vaccine decided to dispatch one million doses to the country, about half of what it had in stock. But where to deploy it is still under debate, says Dominique Legros, a cholera expert at the World Health Organization in Geneva, Switzerland. [ScienceInsider] Editorial

Canada’s Basic Science at Risk of Fading Away, Report Argues

Canada’s scientific enterprise is at risk of sinking to junk bond status as a result of a funding crunch and misguided government and granting council policies, argues a report. In particular, the authors decry a steady shift away from basic science that has left a smaller portion of the nation’s growing scientific community focused on fundamental research. [ScienceInsider] Editorial

Putin Tightens Control over Russian Academy of Sciences

The Russian government has taken further steps to tighten its grip on the Russian Academy of Sciences (RAS) in Moscow. The State Duma—one of the two chambers of the Russian parliament—passed the first draft of a new law that would give president Vladimir Putin the final say in the elections for RAS’s presidency. [ScienceInsider] Editorial

Vaccine Ruling from Europe’s Highest Court Isn’t as Crazy as Scientists Think

The Court of Justice of the European Union in Luxembourg handed down a judgment in a compensation case involving a French man who claimed that a vaccination for hepatitis B caused his multiple sclerosis. The ruling specifies what type of evidence is allowed in EU member states in such cases, but it prompted a flurry of negative press coverage. [Nature News] Editorial

NEW Matrix Biology Europe (MBE) 2018
July 21-24, 2018
Manchester, United Kingdom

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

NEW Postdoctoral Fellow – Mechanobiology of Tissue Repair (St. Michael’s Hospital)

Pharmacology Scientist – Matrix Biology (Symic Bio, Inc.)

Postdoctoral Position – Molecular Genetics (University of Illinois College of Medicine)

Director Position – Stem Cell Biology and Regenerative Medicine (University of Illinois College of Medicine in Chicago)

Postdoctoral Fellow – Gene Regulation in Stem Cells and Tissue Regeneration (Northwestern University)

Assistant Professor – Stem Cell and Regenerative Biology (Harvard University)

Postdoctoral Fellowship – Tissue Fibrosis (University of California, San Francisco)

Group Leaders – Multiple Areas (French National Center for Scientific Research)

Postdoctoral Fellow – Proteoglycan Remodeling (University of Alberta)

Postdoctoral Research Fellow – Tendon and Connective Tissue Biology (Weill Cornell Medical College)

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