Extracellular Matrix News Volume 10.22 | Jun 13 2019

TOP STORY

Hyaluronan Synthase 2-Mediated Hyaluronan Production Mediates Notch1 Activation and Liver Fibrosis

Hyaluronan (HA) production and liver fibrosis were reduced in mice lacking HA synthase 2 (HAS2) in hepatic stellate cells (HSCs), whereas mice overexpressing HAS2 had exacerbated liver fibrosis. HAS2 was transcriptionally up-regulated by transforming growth factor-β through wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, toll-like receptor 4, and newly identified downstream effector Notch1. [Sci Transl Med] Abstract

(Ranked by impact factor of the journal)

Molecular Interactions between Collagen and Fibronectin: A Reciprocal Relationship That Regulates De Novo Fibrillogenesis

To elucidate the potential fibronectin (FN)-collagen (COL) interactions during tissue genesis, scientists explored their co-dependence in vitro by investigating protein binding, conformational changes, assembly kinetics, co-localization, and fiber mechanics. They found that FN accelerated COL nucleation, and in reciprocity, the presence of COL fibrils induced the formation of highly co-localized FN fibrils. [Chem] Abstract | Graphical Abstract

RASA1-Dependent Cellular Export of Collagen IV Controls Blood and Lymphatic Vascular Development

RASA1 was required for endothelial cell (EC) survival during developmental angiogenesis because it was necessary for the export of collagen IV from ECs and deposition in vascular basement membranes. In the absence of RASA1, dysregulated Ras mitogen-activated protein kinase signal transduction in ECs resulted in impaired folding of collagen IV and its retention in the endoplasmic reticulum leading to EC death. [J Clin Invest] Abstract | Full Article

Regenerative and Durable Small-Diameter Graft as an Arterial Conduit

Researchers fabricated small-diameter vascular grafts by electrospinning fibrin tubes and poly(ε-caprolactone) fibrous sheaths, which improved suture retention strength and enabled long-term survival. Using surface topography in a hollow fibrin microfiber tube, they enabled immediate, controlled perfusion and formation of a confluent endothelium within three-four days in vitro with human endothelial colony-forming cells, but a stable endothelium was noticeable at four weeks in vivo. [Proc Natl Acad Sci USA] Abstract

Transcriptomic Analysis Reveals that BMP4 Sensitizes Glioblastoma Tumor-Initiating Cells to Mechanical Cues

The authors showed that tumor-initiating cell (TIC) differentiation induced by bone morphogenetic protein 4 (BMP4) suppressed expression of proteins relevant to ECM signaling and sensitized TIC spreading to matrix stiffness. Notably, stiffness and differentiation modulated oxygen consumption, and inhibition of oxidative phosphorylation influenced cell spreading in a stiffness- and differentiation-dependent manner. [Matrix Biol] Abstract

Increased Matrix Metalloproteinases Expression in Tuberous Sclerosis Complex: Modulation by MicroRNA 146a and 147b In Vitro

Investigators determined whether anti-inflammatory microRNAs miR146a and miR147b, which can regulate gene expression at the transcriptional level, could attenuate dysregulated matrix metalloproteinase and TIMP expression in tuberous sclerosis complex tuber-derived astroglial cultures. [Neuropathol Appl Neurobiol] Abstract

ATR Mediates Cisplatin Resistance in 3D-Cultured Breast Cancer Cells via Translesion DNA Synthesis Modulation

Scientists compared MCF-7 breast cancer cell responses to cisplatin in traditional two-dimensional and in three-dimensional (3D)-reconstituted basement membrane cell culture models. The results showed a substantial increase of cisplatin resistance mediated by the 3D microenvironment. [Cell Death Dis] Full Article

GGA2 and RAB13 Promote Activity-Dependent β1-Integrin Recycling

Functionally, RAB13 silencing triggered the intracellular accumulation of active β1-integrin, and reduced integrin activity in focal adhesions and cell migration similarly to golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) depletion, indicating that both facilitated active β1-integrin recycling to the plasma membrane. [J Cell Sci] Abstract

Infiltrating CCR2⁺ Monocytes and Their Progenies, Fibrocytes, Contribute to Colon Fibrosis by Inhibiting Collagen Degradation through the Production of TIMP-1

In CC chemokine receptor 2 (CCR2)-deficient bone marrow chimeras, monocyte and fibrocyte numbers in the colonic lamina propria significantly decreased, and colon fibrosis was attenuated. In colon tissue, mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 but not of collagen I, transforming growth factor-β1 or matrix metalloproteinases was significantly different between the two chimeras. [Sci Rep] Full Article

Pirfenidone Attenuates Lung Fibrotic Fibroblast Responses to Transforming Growth Factor-β1

Pirfenidone attenuated transforming growth factor-β1- and collagen triple helix repeat containing protein 1(CTHRC1)-induced fibroblast activity, upregulation of bone morphogenic protein-4/gremlin1, and downregulation of α-smooth muscle actin, fibronectin, and four-and-a-half LIM domain protein 2, similar to that observed post-CTHRC1 inhibition. [Respir Res] Full Article

Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells

Researchers found that silencing of fibronectin expression attenuated human RCC 786-O and Caki-1 cell growth and migration. Silencing of potential fibronectin receptor integrin α5 and integrin β1 decreased 786-O cell ability in movement and chemotactic migration. [Int J Mol Sci] Full Article

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Integrins as Biomechanical Sensors of the Microenvironment

The authors provide an overview of how integrin function is regulated from both a biochemical and a mechanical perspective, affecting integrin cell-surface availability, binding properties, activation or clustering. They address how this biomechanical regulation allows integrins to respond to different ECM physicochemical properties and signals, such as rigidity, composition and spatial distribution. [Nat Rev Mol Cell Biol] Abstract

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

OrthoTrophix Presents Clinical Data Demonstrating Significant Correlation between Knee Function Improvement and Cartilage Thickness Increase/Stabilization after TPX-100

OrthoTrophix, Inc. announced that the company and its collaborators are presenting Phase II clinical study data. The presentation, entitled “Improved Knee Physical Function Correlates Significantly with TF Cartilage Thickness Increase after IA TPX-100” is abstract THU0441. [Press release from OrthoTrophix, Inc. discussing research to be presented at the European Congress of Rheumatology 2019, Madrid] Press Release

LulzBot Announces 3D Bioprinting Collaboration with FluidForm

Aleph Objects, Inc. announced their collaboration with FluidForm Inc. Together, Aleph Objects and FluidForm will combine their expertise to offer new bioprinting solutions, with the initial offering coming this summer. 3D bioprinting is already being used in labs to create tissue scaffolds and other complex biological structures. [Aleph Objects, Inc. (Business Wire, Inc.)] Press Release

Servier and Galapagos Complete Enrollment of Global ROCCELLA Phase II Clinical Trial with GLPG1972/S201086 in Knee Osteoarthritis Patients

Servier and Galapagos NV completed recruitment for their ROCCELLA Phase II trial with GLPG1972/S201086, ahead of schedule. GLPG1972/S201086 is a disease-modifying osteoarthritis drug candidate that, in two animal models, has been shown to efficiently target a cartilage degrading enzyme called ADAMTS-5. [Galapagos NV] Press Release

CorMatrix^® Cardiovascular, Inc. Receives FDA 510(k) Clearance to Market the Cor™ PATCH Epicardial Patch for Tissue Support and Repair in Adult Patients

CorMatrix® Cardiovascular, Inc. announced FDA 510(k) clearance for the Cor™ PATCH. The Cor™ PATCH epicardial patch is the first epicardial cardiovascular medical device composed of first next generation CorMatrix^® ECM^® to be cleared by the FDA and introduced into the US cardiac surgery market. [CorMatrix® Cardiovascular, Inc. (PR Newswire Association LLC.)] Press Release

Sudanese Academics Defiant as Revolution Turns Bloody

Sudan’s universities are shut, flights have been suspended and the Internet remains almost entirely blocked after a brutal crackdown in which paramilitaries are thought to have killed some 100 pro-democracy protestors. But none of this has dented the resolve of the protestors, whose ranks include several prominent academics and whose demands include freeing universities from government influence. [Nature News] Editorial

Research Institute Investigates Possible Image Manipulation in Papers

India’s Council of Scientific & Industrial Research is investigating potential image-manipulation problems flagged by PubPeer commenters in 130 papers from its Indian Institute of Toxicology Research, The Hindu reported. The publication has separately reported PubPeer comments pointing out apparent image manipulation for 31 papers from the CSIR-Indian Institute of Chemical Biology, and 35 from the CSIR-Central Drug Research Institute. [The Scientist] Editorial

NEW 6^th Annual European Congress on Clinical and Translational Medicine
October 18-20, 2019
Vienna, Austria

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

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

Scientist – Matrix Biology (STEMCELL Techonologies Inc.)

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)

Postdoctoral Researchers – Hydrogel Chemistry & Kidney Tissue Engineering (Murdoch Children’s Research Institute)

Head of School – Biomedical Engineering (University of Sydney)

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

Associate Professor/Professor – Cell & Molecular Biology (University of Illinois at Chicago)

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

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