Extracellular Matrix News Volume 10.23 | Jun 20 2019

TOP STORY

Sesn3 Protects against Diet-Induced Nonalcoholic Steatohepatitis in Mice via Suppression of the TGFβ Signal Transduction

After an eight-week feeding with a nonalcoholic steatohepatitis (NASH)-inducing diet, Sesn3 transgenic mice were largely protected against NASH development. Scientists revealed that multiple ECM related processes were upregulated including TGFβ signaling and collagen production. They illustrated a critical control of the TGFβ-Smad pathway by Sesn3 at the TGFβ receptor and Smad3 levels. [Hepatology] Abstract

(Ranked by impact factor of the journal)

Polydopamine-Based Interfacial Engineering of Extracellular Matrix Hydrogels for Construction and Long-Term Maintenance of Living Three-Dimensional Tissues

Researchers leveraged a single-step surface functionalization technique based on polydopamine to drastically increase the strength of adhesion between hydrogel scaffolds and cell culture substrates. The method was compatible with different types of ECM and polymeric surfaces, and also permitted prolonged shelf storage of functionalized culture substrates. The proof-of-principle of this technique was demonstrated by stable long-term 3D culture of human lung fibroblasts. [ACS Appl Mater Interfaces] Abstract

Three-Dimensional Microenvironmental Priming of Human Mesenchymal Stem Cells in Hydrogels Facilitates Efficient and Rapid Retroviral Gene Transduction via Accelerated Cell Cycle Synchronization

Photocrosslinkable hyaluronic acid (HA) hydrogels with an elastic modulus of 1.0-2.7kPa were prepared by varying the degree of methacrylation in the HA backbone. Culturing human adipose-derived stem cells in a 3D microenvironment significantly reduced the amount of time required for retroviral gene transduction compared with the conventional 2D method and maintained a high transduction efficiency. [NPG Asia Mater] Full Article

Adamts17 Is Involved in Skeletogenesis through Modulation of BMP-Smad1/5/8 Pathway

The hypertrophic zone of the growth plate in a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)17^-/- mice was shortened, with enhanced fibrillin-2 deposition, suggesting increased incorporation of fibrillin-2 into microfibrils. The authors indicated alteration of the bone morphogenetic protein (BMP) signaling pathway after Adamts17 knockout. [Cell Mol Life Sci] Abstract

COL1A2 Is a TBX3 Target that Mediates Its Impact on Fibrosarcoma and Chondrosarcoma Cell Migration

Investigators showed that TBX3 levels were regulated by AKT1 and that pseudo-phosphorylation of TBX3 at an AKT consensus serine site, enhanced its ability to activate COL1A2. Importantly, they demonstrated that COL1A2 mediated the pro- and anti-migratory effects of TBX3 in chondrosarcoma and fibrosarcoma cells respectively. [Cancer Lett] Abstract | Graphical Abstract

Multiplex Quantitative Analysis of Stroma-Mediated Cancer Cell Invasion, Matrix Remodeling, and Drug Response in a 3D Co-Culture Model of Pancreatic Tumor Spheroids and Stellate Cells

Effects of pancreatic stellate cell (PSC) co-culture on ECM fiber network, invasive migration of cancer cells, and expression of epithelial-mesenchymal transition-related proteins were examined. Conditioned media was also analyzed for secreted factors involved in cancer cell-PSC interactions. [J Exp Clin Cancer Res] Full Article

In Vivo Evaluation of Scaffolds Compatible for Colonoid Engraftments onto Injured Mouse Colon Epithelium

When colonoids were transplanted with gelatin, collagen, and fibrin glue into an EDTA colitis mouse model, all groups were found to be successfully engrafted. Fibrin glue, especially, showed significant increase in the engrafted area compared with Matrigel after four weeks. [FASEB J] Abstract

Knockdown of KDM1A Suppresses Tumor Migration and Invasion by Epigenetically Regulating the TIMP1/MMP9 Pathway in Papillary Thyroid Cancer

Lysine demethylase 1A (KDM1A) knockdown inhibited the migration and invasive abilities of papillary thyroid cancer cells both in vitro and in vivo. Researchers identified tissue inhibitor of metalloproteinase 1 (TIMP1) as a key KDM1A target gene. KDM1A activated matrix metalloproteinase 9 (MMP9) through epigenetic repression of TIMP1 expression by demethylating H3K4me2 at the TIMP1 promoter region. [J Cell Mol Med] Full Article

Angiopoietin-Like Protein 8 Expression and Association with Extracellular Matrix Metabolism and Inflammation during Intervertebral Disc Degeneration

Silencing of angiopoietin-like protein 8 (ANGPTL8) attenuated the degradation of the anabolic protein type collagen II, and reduced the expression of the catabolic proteins MMP3 and MMP9, and the inflammatory cytokine IL-6 through inhibition of NF-κB signaling activation. In addition, the effect of ANGPTL8 was evaluated in a rat model of puncture-induced intervertebral disc degeneration. [J Cell Mol Med] Full Article

ID3 Mediates the TGF-β1-Induced Suppression of Matrix Metalloproteinase-1 in Human Granulosa Cells

Scientists demonstrated that transforming growth factor-β1 (TGF-β1) down-regulated the expression and production of matrix metalloproteinase-1 (MMP1) via a TβRII/ALK5-mediated SMAD-dependent signaling pathway in human granulosa-luteinL cells. They showed that the suppressive effect of TGF-β1 on the expression of MMP1 was mediated by a transcription factor, the inhibitor of differentiation 3 (ID3) protein. [FEBS J] Abstract

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Matrix Metalloproteinases: Expression, Regulation and Role in the Immunopathology of Tuberculosis

The authors summarize the recent advancements regarding expression of matrix metalloproteinases in tuberculosis, their immunomodulatory role, as well as their potential as therapeutic targets to control the deadly disease. [Cell Prolif] Full Article

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Prometic Presents New Data on PBI-4050 and Its Mechanism of Action on Kidney Fibrosis

Prometic Life Sciences Inc. announced that four abstracts highlighting Prometic’s progress in developing PBI-4050 as a potential treatment for both acute kidney injury and chronic kidney disease were presented. [Press release from Prometic Life Sciences Inc. discussing research presented at the 56^th Congress of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), Budapest] Press Release

Samumed Doses First Subject in Phase III STRIDES-X-Ray Trial of Lorecivivint for the Treatment of Knee Osteoarthritis

Samumed, LLC announced that it has dosed the first patient in its Phase III STRIDES-X-ray trial of lorecivivint (SM04690), a CLK/DYRK inhibitor that modulates the Wnt pathway, in patients with knee osteoarthritis. The trial is designed to support the development of lorecivivint as a potential disease-modifying osteoarthritis drug. [Samumed, LLC] Press Release

RIBOMIC Announces Positive Top-Line Results from the Phase I/IIa Clinical Trial of RBM-007 (SUSHI Study) in Subjects with Wet Age-Related Macular Degeneration

RIBOMIC, Inc. announced positive top-line results from its SUSHI study, Phase I/IIa single ascending dose clinical study of RBM-007, anti-FGF2 aptamer, in nine subjects with wet age-related macular degeneration. RBM-007 is a novel oligonucleotide-based aptamer with potent anti-fibroblast growth factor 2 activity. [RIBOMIC, Inc.] Press Release

Compelling Positive Results Reported from Human Liver Experiments with ContraVir Pharmaceuticals’ NASH Drug Candidate

ContraVir Pharmaceuticals, Inc. announced findings from its first study with human precision cut liver slice cultures. Co-administration of ContraVir’s clinical phase drug candidate, CRV431, was found to be 100% effective at preventing fibrosis induction beyond baseline levels. CRV431 at clinically relevant concentrations also partially or completely blocked several genetic and protein biomarkers of inflammation and fibrosis. [ContraVir Pharmaceuticals, Inc.] Press Release

Africa’s Science Academy Leads Push for Ethical Data Use

The African Academy of Sciences has started work on the continent’s first cross-disciplinary guidelines on how to collect, store and share research data and specimens in ways that protect study participants from exploitation and benefit African citizens. [Nature News] Editorial

Trump Issues Executive Order that Could Reduce Scientific Advice

President Donald Trump issued an executive order on June 14 to cut back the number of advisory committees by at least a third by the end of September, according to a statement from the White House. The federal advisory committee system is the formal structure for government agencies to seek advice from experts including scientists. [The Scientist] Editorial

China Clamps Down on Foreign Use of Chinese Genetic Material and Data

China has announced new regulations for the use of human genetic resources that come from Chinese participants. The rules, announced on June 10, require international scientists using biomaterials from China to have a Chinese collaborator and go into effect on July 1. [The Scientist] Editorial

NEW The Copenhagen Bioscience Conference on Intestinal Organoids
September 29-October 2, 2019
Copenhagen, Denmark

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

NEW Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

NEW Postdoctoral Postions – Tissue Engineering (University of Oslo)

Scientist – Matrix Biology (STEMCELL Techonologies Inc.)

Faculty Positions – Biochemistry & Molecular Biophysics (Washington University in St. Louis School of Medicine)

Postdoctoral Position – Bioengineering Cell Fate & Morphogeneis in Organoids (KU Leuven)

Postdoctoral Research Fellowships – Kidney Disease (Vanderbilt University Medical Center)

Postdoctoral Position – Experimental Systems Biology of Lung Regeneration & Fibrosis (Helmholtz Zentrum München)

Head of School – Biomedical Engineering (University of Sydney)

Postdoctoral Fellowship – Renal Extracellular Matrix Research (Vanderbilt University Medical Center)

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

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