U Illinois research team finds damaged liver cells reprogram to regenerate

Biochemistry professor Auinash Kalsotra, second from left, and his team, including, from left, graduate students Waqar Arif, Joseph Seimetz and Sushant Bangru, uncovered the molecular underpinnings of liver regeneration.
(Photo by L. Brian Stauffer via illinois.edu)

New research led by an Indian-American professor at the University of Illinois has discovered how damaged liver cells repair themselves through a signal and return to an early stage of their own development.

The findings of the team led by U, of I. biochemistry professor Auinash Kalsotra, are reported in the journal Nature Structural & Molecular Biology, according to a Sept. 26, press release from the university.

“The liver is a resilient organ,” said Professor Kalsotra, quoted in the press release. “It can restore up to 70 percent of lost mass and function after just a few weeks. While it is known that in a healthy adult liver the cells are dormant and rarely undergo cell division Kalsotra said, “However, if the liver is damaged, the liver cells re-enter the cell cycle to divide and produce more of themselves.”

The human liver can become chronically damaged by toxins such as alcohol and even certain medicines, but still continue to function and self-repair, Kalsotra said.

The research looked at the molecular level to determine what was happening in a damaged liver allowing it to regenerate while still performing normal functions. The team which consisted of Kalsotra as well as graduate students Sushant Bangru, Waqar Arif, and Joseph Seimetz, used a mouse model of a liver severely damaged by toxins. they compared injured adult liver cells with healthy cells present during a stage of development just after birth “and found that injured cells undergo a partial reprogramming that returns them to a neonatal state of gene expression,” the press release noted.

The repair and regeneration was the result of fragments of messenger RNA, the molecular blueprints for proteins, rearranging and regenerating liver cells in a process similar to the neonatal period of development.

“We found that the liver cells after birth use a specific RNA-binding protein called ESRP2 to generate the right assortment of alternatively spliced RNAs that can produce the protein products necessary for meeting the functional demands of the adult liver,” Sushant Bangru, the lead author of the study, is quoted saying in the press release. “When damaged, the liver cells lower the quantity of ESRP2 protein. This reactivates fetal RNA splicing in what is called the ‘Hippo signaling pathway,’ giving it instructions about how to restore and repopulate the liver with new and healthy cells,” Bangru explained further.

The National Institutes of Health, March of Dimes and American Heart Association supported this research.





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