We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Rare Inherited Enzyme Disorder Yields Insight into Fibrosis

By LabMedica International staff writers
Posted on 31 Jul 2019
Print article
Image: The LSRFortessa flow cytometer instrument (Photo courtesy of BD Biosciences).
Image: The LSRFortessa flow cytometer instrument (Photo courtesy of BD Biosciences).
Mammalian tissues and organs preserve their structural and functional homeostasis by means of their supportive connective tissue, a three-dimensional network of cells and extracellular matrix (ECM) with different topological characteristics depending on the organ/tissue in which it is embedded.

An association has been discovered between a deficiency in the enzyme neuraminidase 1 (NEU1) and the build-up of connective tissue (fibrosis) in organs such as the muscle, kidney, liver, heart and lungs. Fibrosis includes life-threatening conditions such as idiopathic pulmonary fibrosis.

An international team of scientists working with the St. Jude Children’s Research Hospital (Memphis, TN, USA) addressed the potential involvement of NEU1 in human fibrosis, they first determined by Masson’s trichrome staining that the fibrotic disease seen in the muscle was a general phenotype of the Neu1−/− connective tissue in different organs. They checked tissue from 89 adults with idiopathic pulmonary fibrosis (IPF) and found NEU1 production was significantly down-regulated as compared to adults without the diagnosis.

Initially the team used a mouse model before confirming their results in human cells. Human lung fibroblasts from control individuals and patients with IPF were obtained and cultured. Fluorescence-activated cell sorting analyses of skeletal muscle connective tissue cells were performed using markers specific on an LSRFortessa flow cytometer instrument. Proliferation assays were performed and every 24 hours for 1 to 4 days and the optical density was read at 490 nm (OD490) with a FLUOstar Omega plate reader. Other methods used in the study included real-time quantitative polymerase chain reaction, immunohistochemistry, exosome isolation, sucrose gradient, proteomics, and size distribution.

The team found that mouse fibroblasts lacking NEU 1 release excessive numbers of molecules that degrade the extracellular matrix, as well as exosomes. The exosomes are loaded with factors that promote fibrosis, including the growth factor TGF-β and the signaling molecule WNT. Normal mouse and human fibroblasts cells were activated to proliferate and migrate when exposed to exosomes containing TGF-β, WNT and related molecules released by NEU1-deficient fibroblasts. The investigators checked an RNA sequencing database of 89 idiopathic pulmonary fibrosis patients and found NEU1 was among the most down-regulated of 66 genes included in the database.

Alessandra d'Azzo, PhD, the senior author of study said, “This is the first time NEU1 has been associated with fibrotic conditions. NEU1 is an important enzyme that breaks down sugar-containing molecules in many cells of the body, but it has not really been on the radar for adult health problems.” The authors concluded that their findings reveal an unexpected exosome-mediated signaling pathway downstream of NEU1 deficiency that propagates a fibrotic disease and could be implicated in idiopathic forms of fibrosis in humans. The study was published on July 17, 2019, in the journal Science Advances.

Related Links:
St. Jude Children’s Research Hospital

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
One Step HbA1c Measuring System
GREENCARE A1c
Anti-Cyclic Citrullinated Peptide Test
GPP-100 Anti-CCP Kit
Gold Member
Reagent Reservoirs
Reagent Reservoirs

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The study showed the blood-based cancer screening test detects 83% of people with colorectal cancer with specificity of 90% (Photo courtesy of Guardant Health)

Blood Test Shows 83% Accuracy for Detecting Colorectal Cancer

Colorectal cancer is the second biggest cause of cancer deaths among adults in the U.S., with forecasts suggesting 53,010 people might die from it in 2024. While fewer older adults are dying from this... Read more

Hematology

view channel
Image: The Gazelle Hb Variant Test (Photo courtesy of Hemex Health)

First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy

Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read more

Microbiology

view channel
Image: The new platform is designed to perform blood-based diagnoses of nontuberculosis mycobacteria (Photo courtesy of 123RF)

New Blood Test Cuts Diagnosis Time for Nontuberculous Mycobacteria Infections from Months to Hours

Breathing in nontuberculous mycobacteria (NTM) is a common experience for many people. These bacteria are present in water systems, soil, and dust all over the world and usually don't cause any problems.... Read more

Industry

view channel
Image: These new assays are being developed for use on the recently introduced DxI 9000 Immunoassay Analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter and Fujirebio Expand Partnership on Neurodegenerative Disease Diagnostics

Beckman Coulter Diagnostics (Brea, CA, USA) and Fujirebio Diagnostics (Tokyo, Japan) have expanded their partnership focused on the development, manufacturing and clinical adoption of neurodegenerative... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.