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Study: Tissue regeneration can be promoted by inactivating a certain-protein coding gene

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 Researchers have reported in a recent study that regeneration of liver tissues in mammals is enhanced by the inactivation of a certain protein-coding gene. The research was conducted at the Children's Medical Center Research Institute at UT Southwestern (CRI). The study was published in the journal Cell Stem Cell.

"This research gives us ideas about new ways to treat liver damage or chronic liver disease," said senior author Dr. Hao Zhu, an Assistant Professor at CRI with joint appointments in Internal Medicine and Pediatrics at UT Southwestern Medical Center. 

Dr Zhu explains that unlike tails in lizards and arms in starfish have the ability to regrow, mammals have partially lost the capability of regenerating body parts. The liver of humans is a unique organ that has the capability to regenerate up to 70 percent of its tissue after an injury. However, if the liver is damaged repeatedly by the chemical toxins or chronic disease, the ability of regeneration is lost. Formation of cirrhosis or scar tissue takes place which also increases the risk of cancer said, Dr. Zhu, who also treats patients with liver cancer at Parkland Memorial Hospital. 

Deaths caused due to liver cancer have increased with the highest rate among all the cancers from 2003-2012, reports The National Cancer Institute (NCI). The risk factors for liver cancer apart from cirrhosis includes chronic liver disease, infections caused by the hepatitis C virus (HCV), liver damage from alcohol or other toxins and some rare genetic disorders.

In the study, Dr Zhu used a mouse for his investigation that lacked Arid1a, this gene is associated with some human cancers. 

"In humans, the gene ARID1A is mutated in several cancers, including liver cancer, pancreatic cancer, breast cancer, endometrial cancer, lung cancer, the list goes on," Dr. Zhu said. "It is not mutated in every type of cancer, but in a significant number. Those mutations are found in 10 to 20 percent of all cancers, and the mutations render the gene inactive."

It was assumed that the mice lacking with Arid1a would be going through a liver damage and subsequently liver cancer. In fact, the opposite came true and they observed that there was no damage caused to the liver. He also added that in the mice, regeneration of liver was much faster with better functioning. 

"The livers were resistant to tissue damage and healed better, which are two good things -- like playing offense and defense at the same time," he said. "These results opened up a whole new avenue of investigation for us, and through that investigation we found a new function for this gene."

 

Liver in the mice appeared healthier on observation and even the blood tests confirmed the improved functioning of the liver. The researchers found that deletion of gene in the mice with many liver injuries leads to a quicker replacement of the tissue mass and in response to a chemical injury also reduces fibrosis. Even the wounded skin was quickly healed in a mice that lacked the Arid1a gene. 

Till now there are no drugs that can mimic a lack of the protein, but a researchers are to search for one by taking a grant from Cancer Prevention and Research Institute of Texas (CPRIT).

"We want to identify small molecules that mimic the effect of these genetic findings. The ideal drug would be one that helps the liver heal while inhibiting the development of cancer. That would be the perfect drug for my patients," said Dr. Zhu, a CPRIT Scholar in Cancer Research.

"Somehow, loss of this gene seems to make it easier for the cell to go back and forth," said Dr. Zhu,  "This study opens up new areas to investigate how to rejuvenate tissues without necessarily increasing cancer risk, although many more tests will have to be done to determine how the risk of all types of liver cancers are altered."

According to Pharmaion, pharma and healthcare consultants, the recent study has demonstrated that the deletion or inactivation of the gene Arid1a leads to more healing and enhances tissue regeneration. This study also opens up the door for more research on developing drugs that can mimic the same effect. 

 

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