Protein That Stops Cell Division Could Serve as a Biomarker or Therapeutic Target for Liver Disease

 

 

      According to recent research published in The FASEB Journal, a protein that stops the cells from dividing in response to damage or stress could become a new biomarker or therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD). This protein is called cyclin-dependent kinase inhibitor 1A (CDKN1A), it was upregulated in patient datasets and models in animals of the disease, and the expression level correlated with the severity of the disease in the study. 

    With current technologies, only liver biopsies or medical imaging methods such as ultrasounds are used to diagnose MALSD, and no medication has been approved to treat the disease yet. To find a diagnostic biomarker or drug target, the researchers used bioinformatics methods to analyze public patient datasets for differentially regulated genes in MASLD patients and compared them with controls. They found that CDKN1A was upregulated in all of the datasets obtained. The study states that: 

"The protein encoded by this gene responds to cell stress and damage by preventing cells from dividing, shifting them to a senescent or inactive state. Further analysis of five patient datasets, including the initial three, demonstrated that CDKN1A transcript levels increased with disease severity."

    The expression of CDKN1A positively correlated with two clinical assessments: the disease's activity score and the fibrosis stage. In the patients' liver tissue, immunofluorescence staining showed the protein's higher expression compared to tissues from the control group. 

    The results from the study are consistent with previous reports, which suggest an association between CDKN1A and MASLD. The researcher said: 

“Functionally, CDKN1A may contribute to MASLD progression by promoting hepatocyte senescence, exacerbating lipid toxicity, and fostering chronic inflammation and fibrosis,”

    These findings will guide the study to a more effective way of using biomarkers for disease diagnosis and therapeutic intervention. 

WORKS CITED

MBT Desk (2025). Protein That Stops Cell Division Could Serve as a Biomarker or Therapeutic Target for Liver Disease. MedBound Times. https://www.medboundtimes.com/biotechnology/cdkn1a-as-biomarker-therapeutic-target-in-masld?utm_source=website&utm_medium=related-stories

Deng, L., Deng, J., Luo, L., et al. (2025). Identification of CDKN1A as a potential key risk factor in MASLD progression. FASEB. https://doi.org/10.1096/fj.202402942R

Beethoven: What Truly Caused His Death?

  Just imagine being able to go back in time and meeting any of your favorite idols. Unfortunately, this is not possible, but we can learn a lot about them in various ways, especially with surviving samples of their DNA. The well-renown German composer, Ludwig Van Beethoven, had multiple locks of his hair (some samples shown to be inauthentic or inconclusive) passed down from generation to generation. Tristen Begg and other researchers from the University of Cambridge (starting in 2014) analyzed the authentic samples to better understand the factors behind his death (known to be plagued by various health problems throughout his lifetime). After reconstructing Beethoven's genome, the research team was able to not only find a gene variant (PNPLA3) which increases the risks of liver disease but also traces of Hepatitis B (further increasing his susceptibility to infection).

  With all the evidence provided, it's logical to assume this is how he died. Especially, considering the fact nearing his death, he was a heavy drinker which would have caused additional damage unto his liver. Yet, what if the hair provided was not from Beethoven? It was found that the Y-chromosome in the samples were inconsistent with living relatives of an ancestor of Beethoven. Does that mean all that work was meaningless? Not exactly. As shown from within the article, one of Beethoven's ancestor's (paternal side) may have had a child outside of marriage. It's a plausible presumption and could further build onto what we know about his ancestry. If we had more DNA samples from famous figures in the past, imagine how much further we could delve into the unknowns of history.

Links

- https://www.sciencenews.org/article/beethoven-hair-dna-composer-death

- https://www.cell.com/current-biology/fulltext/S0960-9822(23)00181-1

Protein to Help Liver Regeneration

In an article recently published this week talks about how a protein, GF21, encourages regeneration in mice carrying the human liver regeneration protein.  The human form of the protein tends to not be very active, especially after a transplant or damage from alcohol consumption.

The study showed that after experiencing liver damage, mice were able to regain original liver mass in approximately ten days, while mice with the human protein had no change after three months.   Providing GF21 allowed their liver to regain mass.  The mouse version of this protein causes cancer, meaning that there is no way they would try to modify the human protein to be the same.  In addition, the human gene is usually targeted in cholesterol treatment; another reason why the liver may struggle to regenerate.

Reading how giving a certain protein can cause the liver the regenerate is really interesting.  I know people who have liver damage and struggle, so the idea of them being able to have a slightly easier situation because of a treatment is amazing.  It's interesting to think that a slight difference in genetic coding could cause two similar proteins to be so different that one can regenerate, while the other can't.

Secondary Link: http://ucdmc.ucdavis.edu/publish/news/newsroom/9856

Breaking Bad Mitichondria

In this article, researchers have identified a mechanism that explains why people with the Hepatitis c virus get liver disease and why the virus is able to persist i the body for so long. The pathogen attacks the liver cells energy centers, mitochondria, which does not allow for the cell to fight off infections or diseases. Hepatitis c causes liver cancer. After the mitochondria are done being attacked the proteins tell the mitochondria to eliminate the damaged area, but the process to repair ends up aiding the virus making things worse. Mitochondria convert food onto a form of energy which is used by the cells. The virus stimulates the production of protein that induces viral damaged mitochondria. Although mitochondria help with fighting off the infections and diseases it also helps with keeping the virus infected cell alive. The virus is able to use the mitochondria to keep reproducing new cells and amino acids to help fuel its continuous replication and virulence. Understanding mitochondria is what keeps the virus going when attaining the hepatitis c disease.


http://jcs.biologists.org/content/123/9/1389.abstract

Gene Editing in Adult Mice

Researchers at the Massachusetts Institute of Technology have cured mice that had a single-gene mutation which caused a rare liver disease. Inserting DNA is a fairly simple task while making changes later in embryonic development proves to be much more difficult, especially editing an existing gene. Tyrosinemia is a rare, autosomal recessive disorder which affects the livers ability to break down the amino acid tyrosine. The disease is a single mutation that encodes the enzyme fumarylacetoacetate hydrolase (Fah).
DNA of bacteria have the ability to target and snip DNA of viruses; this was the system that was used in this research. Programmed cells were injected into adult mice were the Fah mutation was corrected. This has been done before in an embryonic stage of development but never in a full grown adult. This is the first successful gene editing done in an adult animal and proves to be a huge step for this research and gives hope that eventually this will be useful technique for humans.
Problems with this technique include getting a wrong portion of DNA cut which could cause extensive damage. Scientist are working was to safely and efficiently use this technique.

For more information on Tyrosinemia visit the Genetics Home Reference web page. 
Original Article:  Digital Journal

Identification of genes associated with unhealthy liver function

NAFLD Diagram of what the liver will look like 

Picture of what a Fatty Liver and NASH looks like

In a study led by Translational Genomics Research Institute (TGen), 2,300 extremely obese diabetes patients have been identified with genes that are shown to associate with an unhealthy liver function. These patients that were part of the study were enrolled in a bariatric surgery program which is the removal of parts of the stomach and small intestines to induce weight loss. In the experiment, results were shown on the markers that were placed on the neurocan gene on chromosome 19p12 and rs2501843 on chromosome 1. Also, TGen expresses that the genome-wide analysis identifies loci associated with total bilirubin levels, steatosis, and mild fibrosis in nonalcoholic fatty liver disease. ” It has been believed that these are genetic factors that could help with identifying patients who are at risk and is the nation’s first large scale genome-wide association study for overweight patients with diabetes. Dr. Glenn S. Gerhard, a faculty member of the Geisinger Obesity Institute and a co-investigator of the study, added “The evidence for the new genetic loci may even play a role in biological mechanisms for NAFLD and NASH.”  Dr. Johanna DiStefano, the study's principal investigator and lead author, agrees with stating “These genetic factors could help us identify patients who are most at risk of developing non-alcoholic forms of fatty-liver disease (NAFLD), and which patients may be more likely to progress to severe forms of NAFLD, such as steatohepatitis (NASH). Overall, both doctors are in agreement that by identifying these genetic loci in diabetes patients, it has helped doctors evaluate patients who are at risk and require a transplant. This buildup of extra fat in liver cells, NAFLD, is one of the most common causes of chronic liver disease and could result in severe insulin resistance or metabolic syndromes. Before reaching these stages, identifying these genes before hand can help doctors diagnose patients with an unhealthy liver function in early stages rather than before NAFLD is classified or even worse NASH.     

(Article) http://www.medicalnewstoday.com/releases/266929.php

http://www.liverfoundation.org/abouttheliver/info/nafld/

Genetics Defines a Distinct Liver Disease

In a study described by an article in Science Daily, it has been revealed that researchers have associated nine genetic regions with a rare autoimmune disease of the liver known as primary sclerosing cholangitis (PSC).  According to The American Liver Foundation, (PSC) is a chronic, or long-term, disease that slowly damages the bile ducts inside and outside the liver.

Approximately 70 per cent of people who suffer from PSC also suffer from IBD. The team showed that only half of the newly associated genetic regions were shared with inflammatory bowel disease (IBD). For the first time, this definitively proves that PSC, although genetically related to IBD, is a distinct disease by itself. There are no effective treatments available. Although PSC affects only one in 10,000 people, it is a leading cause of liver transplant surgery.

This study has discovered the underlying genetic aspects of PSC, more than ever before.

According to the article,

“Using the Immunochip genotyping chip, we can pull apart the genetic relationships between these autoimmune diseases and begin to see not only their genetic similarities, but also the differences,” says Jimmy Liu, PhD student and first author from the Wellcome Trust Sanger Institute. “As PSC is a rare disorder, sample collection is more difficult than for other, more common, autoimmune diseases. We hope that with more samples from patients, we’ll be able to link more genetic regions to the disease, and it will become easier to identify underlying pathways that could act as therapeutic targets.”