-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
This astonishing discovery changed the direction
of liver disease treatment.
of liver disease treatment.
Researchers from the Walter and Eliza Hall Institute (WEHI) have shown that common liver disease is not caused
by the death of inflammatory cells as previously thought.
This discovery resolves long-standing controversies in gastroenterology and points to new directions
for treatment.
The team studied hepatitis B and nonalcoholic fatty liver disease, two liver diseases that affect billions of people worldwide, to discover what drives their development
.
Their astonishing discovery — the inability of liver cells to experience an inflammatory type of cell death known as "necrosis" — addresses key unsolved questions in the field and will guide the development of
new therapeutic interventions.
Liver tissue samples show typical features of liver disease, despite the lack of key genes
required for necrosis.
WEHI researchers have revealed for the first time that an important type of liver cell cannot undergo necrosis, eliminating this type of cell death as a driver of common liver disease
.
This surprising finding identifies the role and relevance
of necrosis in non-cancerous liver disease.
Non-cancerous liver disease affects billions of people
worldwide.
The findings will help inform the development of new strategies for the treatment of these liver diseasesThe results of this study clarify the controversial role of necrosis in the progression of liver pathology and provide fundamental insights to guide future preclinical and clinical research in new directions
The study was led by lead researcher Dr Marcel Doerflinger, former WEHI PhD researcher Dr Simon Preston and lead researcher Professor Marc Pellegrini, in collaboration
with researchers from the Peter Doherty Institute of Infection and Immunology and the University of Queensland.
Liver disease is a serious and growing health burden
worldwide.
More than 30% of the world's population has nonalcoholic fatty liver disease, the most common liver disease, while 296 million people worldwide have hepatitis
B.
Until now, researchers have believed that necrosis is critical to
the development of these diseases.
However, it is unclear whether this cell death occurs in liver cells or in immune cells that enter the liver due to infection or
diet-related damage.
"We sought to address this research gap and determine the role and relevance of necrosis in common liver disease," said
Dr.
Doerflinger, who led the study.
The researchers used several preclinical genetic models of liver diseases, including nonalcoholic fatty liver disease and its advanced forms, nonalcoholic steatohepatitis, and hepatitis
B.
The team removed key genes needed for necrosis from liver cells to see the impact
on disease development.
They found that deleting these genes made little or no difference, and disease progression proved comparable
to normal liver cells.
This suggests that necrosis is not
associated with the development of these liver pathologies.
"The liver is a vital organ because it plays an important role in the body's metabolism and detoxification processes," says
Dr.
Doerflinger.
"It is unclear why necrosis in liver tissue is suppressed, but we speculate that this may be because the liver is constantly bathed in necrosis signals, such as gut microbial products, so limiting necrosis may protect the liver from excessive inflammation
.
"
The study also revealed the molecular mechanisms
that prevent liver cells from developing necrosis.
After genetic analysis of human liver tissue samples, the team found that liver cells could not produce RIPK3
, a protein that is essential for necrosis.
Production of the RIPK3 protein is limited at the genetic level, and the RIPK3 gene is blocked by an epigenetic modification called "methylation
.
"
"Methylation acts as a gene blockade, preventing the body's protein production machinery from binding to DNA to produce the RIPK3 protein," Dr.
Doerflinger said
.
"Therefore, without this necessary protein to perform its necrotic function, the cell death pathway cannot be initiated
.
"
Dr.
Doerflinger said RIPK3 inhibitors have been growing in terms of potential treatments for liver disease, but their potential clinical use has been limited
due to a lack of fundamental insights.
"These findings are core data to address many unanswered questions in the field and will guide future preclinical trials and clinical studies
in this direction," he said.
Reference: Epigenetic Silencing of RIPK3 in Hepatocytes Prevents MLKL-mediated Necroptosis From Contributing to Liver Pathologies
