MHH research team clarifies how liver inflammation and scarring of liver tissue are connected

At least five million people in Germany suffer from liver disease. Fibrosis, the pathological proliferation of connective tissue, plays an important role in many complications of chronic liver problems. Activated hepatic stellate cells (HSCs) are massively involved in this tissue remodelling. An international research team led by Ingmar Mederacke, Managing Senior Physician at the Department of Gastroenterology, Hepatology and Endocrinology at the Hannover Medical School (MHH) has now found an approach to lower the activation of HSCs and reduce the associated development of liver fibrosis. The work has been published in the renowned journal Science Translational Medicine.

Hepatic stellate cells produce connective tissue

Liver fibrosis and the end-stage of liver fibrosis, cirrhosis, are a significant medical problem for which there are as yet no suitable drugs. The best-known causes include chronic alcohol consumption, infection with hepatitis viruses, but also medication or a fatty liver. The pathogenic stimuli damage the liver cells, the so-called hepatocytes. They die and thus trigger an inflammatory reaction. Until now, it was not known how this inflammatory process activates the hepatic stellate cells. The HSCs are located in the blood vessel walls in the immediate vicinity of the hepatocytes, where they mainly store vitamin A when at rest. However, when they are activated, they transform into myofibroblasts and produce abnormally large amounts of connective tissue. “We looked at which substances are released during cell death of hepatocytes and how exactly these molecules are related to fibrosis formation,” says Professor Mederacke. The research team found out that certain stored, activated sugar molecules (UDP-glucose and UDP-galactose) are released during hepatocyte cell death. These can bind precisely to a protein called P2Y14 as so-called ligands. “We have found the P2Y14 receptor primarily in the liver stellate cells,” explains the physician.

P2Y14 receptor as a link between cell death and fibrosis formation

In the mouse model, the research team examined the signalling pathway between P2Y14 ligands and receptor. An increased release of these activated sugar molecules led to the activation of stellate cells. Inactivation of the P2Y14 receptor, on the other hand, reduced fibrosis formation. “We were also able to detect the P2Y14 receptor in human hepatic stellate cells using special antibodies,” says the hepatologist. The connection between cell death of the liver tissue and fibrosis formation has also been confirmed in studies of healthy and diseased human livers. The discovery could be an important step towards an anti-fibrotic therapy. The next step is to find an antagonist that can block the P2Y14 receptor and thus reduce the development of liver fibrosis.

TECH NEWS RELATED

With changing climate, global lake evaporation loss larger than previously thought

Credit: Unsplash/CC0 Public Domain A white mineral ring as tall as the Statue of Liberty creeps up the steep shoreline of Lake Mead, a Colorado River reservoir just east of Las Vegas on the Nevada-Arizona border. It is the country’s largest reservoir, and it’s draining rapidly. With much of ...

View more: With changing climate, global lake evaporation loss larger than previously thought

Falling stardust, wobbly jets explain blinking gamma ray bursts

Jet (in red) wobbles inside the collapsar before punching out into the photosphere. Credit: Ore Gottlieb/Northwestern University A Northwestern University-led team of astrophysicists has developed the first-ever full 3D simulation of an entire evolution of a jet formed by a collapsing star, or a “collapsar.” Because these jets generate ...

View more: Falling stardust, wobbly jets explain blinking gamma ray bursts

NASA mission aims to study ice and water on the moon's surface

Credit: NASA In the fall of 2023, a U.S. rover will land at the south pole of the moon. Its mission: to explore the water ice that scientists know lurks within the lunar shadows, and which they believe could help sustain humans who may one day explore the moon ...

View more: NASA mission aims to study ice and water on the moon's surface

Assigning moving features in high-speed atomic force microscopy

Graphical abstract. Credit: Biophysics and Physicobiology (2022). DOI: 10.2142/biophysico.bppb-v19.0016 Researchers at Kanazawa University report in Biophysics and Physicobiology how to optimize high-speed atomic force microscopy experiments on live cell membranes, so that moving objects like molecules can be properly followed from frame to frame. In video microscopy techniques, a ...

View more: Assigning moving features in high-speed atomic force microscopy

Rescuing an ancient fish species on the brink of extinction

Credit: Dalhousie University At the base of a winding staircase and tucked away in a dimly lit room, about a hundred healthy fish represent the last, best hope for an ancient species on the brink of extinction. Set against a concrete wall lined with black water pipes and the ...

View more: Rescuing an ancient fish species on the brink of extinction

Life in the Earth's interior is as productive as in some ocean waters

Authors in the field taking samples. Credit: Friedrich-Schiller University Jena Terrestrial and marine habitats have been considered the ecosystems with the highest primary production on Earth by far. Microscopic algae in the upper layers of the oceans and plants on land bind atmospheric carbon (CO2) and produce plant material ...

View more: Life in the Earth's interior is as productive as in some ocean waters

Nanoscale Structures and Thermal Conductivity Link Revealed in Amorphous Silicon

(Photo : Wikimedia Commons/Dr. Anatoly) Luminescent microphotography of amorphous silicon dioxide (SiO2). UV microscopy, fluorescing screen, magnification 200X. Theoretical scientists recently applied topological mathematics and machine learning to determine a hidden link between nanoscale structures and thermal conductivity in amorphous silicon, a glassy material form without repeating crystalline order. ...

View more: Nanoscale Structures and Thermal Conductivity Link Revealed in Amorphous Silicon

Keeping Food on the Table in a Warming World: Bolstering Plant Immunity Against the Heat

Global warming weakens certain plant defenses and makes plants more prone to infections. New research helps explain why, and how to help them fight back. (Pictured: Corresponding author Sheng-Yang He.) Credit: Michigan State University Climate change is making plants more susceptible to disease. New research could help them fight ...

View more: Keeping Food on the Table in a Warming World: Bolstering Plant Immunity Against the Heat

Bubbles and Ultrasound: Novel Technique Kills Cancer Cells

Fertilizers from composting plants contain large quantities of biodegradable plastics

Destruction and recovery of kelp forests driven by changes in sea urchin behavior

Climate change is making plants more vulnerable to disease. New research could help them fight back.

Iceland volcano eruption opens a rare window into the Earth beneath our feet

Ice Age wolf DNA reveals dogs trace ancestry to two separate wolf populations

New single-mode semiconductor laser delivers power with scalability

Researchers screen out herb Bletilla populations with excellent germplasm and important phenotypic traits

How fruit flies lay off the extra salty snacks

Australia prioritizes reducing emissions and cheaper EVs

Controversy Continues Over Whether Hot Water Freezes Faster Than Cold

Higgs boson was discovered 10 years ago. What have we learned about it since then?

OTHER TECH NEWS

Top Car News Car News