Vital protein discovered for liver regeneration

Mariam Ali

Liver disease is the third leading cause of premature death. In the UK alone, over 40 people die from liver diseases every day. For many patients, a liver transplant is usually the last resort to improve their quality of life, with over 2633 on the waiting list. The liver regenerative process is vital for the successful treatment and recovery of a patient, after a transplant procedure. Therefore, a better understanding of liver regeneration could impact an array of the treatments used today. In mammals, the liver has the capacity to regenerate its own tissue through an organized sequence of events. The liver undergoes regeneration after events such as resection, trauma, transplant or hepatic surgery. 

Liver regeneration restores liver mass and involves the proliferation of hepatocytes. The process requires elements such as growth factors, matrix remodelling, cytokines and growth inhibition feedback loops. The organ manages to restore hepatic mass whilst controlling glucose homeostasis throughout the entire regenerative process. It has been possible to investigate liver regeneration using animal models. Most commonly, this has been studied by surgically removing 2/3 of the liver mass in mice, a technique known as partial hepatectomy. A study found that the protein, Annexin A6 (AnxA6), is vital for liver regeneration in mice. AnxA6 happens to be one of the most abundant proteins in the liver.

AnxA6 is not involved in proliferation of hepatocytes during regeneration, but its absence still resulted in high mortality rates amongst mice models. How did this occur?

The removal of hepatic tissue induces “acute proliferative and metabolic stress”. Consequently, the mice had a dramatic depletion of glycogen stores. In these conditions, the liver shifts to synthesising glucose from alanine precursors, to provide energy to perform its necessary functions. The lack of AnxA6 impairs this pathway, and compromises the liver’s capacity to regenerate. This results in further complications and eventually death.

Mice without AnxA6, had an irreversible drop in their blood glucose levels. Even after being supplemented with alanine precursors, the mice’s primary hepatocytes failed to synthesize glucose. This confirms the importance of AnxA6 in driving alanine-dependant gluconeogenesis. The experiment further confirmed this by reinserting the protein into the liver tissue using genetic therapy. Re-establishing the expression of AnxA6 restored the mouse’s survival and allowed for the regenerative process to continue.

These findings shed light on how Annexin A6 is crucial in maintaining glucose homeostasis and survival during liver regeneration. It is a highly relevant finding for the many patients diagnosed with liver disease, worldwide. This may impact future therapeutic strategies for treating liver damage. It is important to note, however, that this is only a possibility and requires further investigation.

References: 
1. https://britishlivertrust.org.uk/about-us/media-centre/statistics/
2.https://www.organdonation.nhs.uk/helping-you-to-decide/about-organ-donation/statistics-about-organ-donation/
3. https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.21172
4. https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.31232

Comments

  1. Anthony Constantinou CEO CWM FX16 March 2022 at 14:36

    Anthony Constantinou | Anthony Constantinou CEO CWM FX says Well the actual cost of the liver transplant is probably depends on how intensive and what complications occur during surgery. It would definitely cost you thousands of dollars. However if you want to know the exact price for this treatment, that would give you the exact detail.

    ReplyDelete

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