Nav: Home

Protein may improve liver regeneration

March 31, 2015

(SACRAMENTO, Calif.) -- Researchers at UC Davis have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPARα, which activates liver regeneration. Normally, mouse PPARα is far more active and efficient than the human form, allowing mice to quickly regenerate damaged livers. However, the research shows that protein fibroblast growth factor 21 (FGF21) can boost the regenerative effects of human PPARα. The findings suggest that the molecule could offer significant therapeutic benefits for patients who have had a liver transplant or suffer from liver disease. The study was published in the journal Oncotarget.

"We found that FGF21 is a good rescuing molecule that facilitates liver regeneration and perhaps tissue repair," said Yu-Jui Yvonne Wan, vice chair for research in the Department of Pathology and Laboratory Medicine at UC Davis and senior author on the paper. "Our data suggests that FGF21 could help with liver regeneration, either after removal or after damage caused by alcohol or a virus."

In the study, human and mouse PPARα showed different capacities for liver regeneration after surgery. Even after having two-thirds of their livers removed, normal mice regained their original liver mass within seven to 10 days. By contrast, mice with human PPARα never fully regenerated, even after three months. However, by increasing FGF21, the team boosted human PPARα's ability to regenerate and heal mouse livers.

While mouse PPARα has regenerative advantages over the human version, there is also a downside, as this ability can lead to cancer. Human PPARα does not cause cancer; however, as noted, it cannot match the mouse protein's regenerative capacity. This trade-off provides a number of advantages on the human side. For example, several popular drugs target PPARα to treat high cholesterol and triglycerides.

Still, in the right context, a more active human PPARα could be a great boon for patients with liver conditions. Using FGF21 to boost this regenerative capacity is an important step in that direction.

These results also add another line to FGF21's impressive resume. In addition to boosting human PPARα's regenerative impact on the liver, the protein has been shown to alleviate insulin resistance, accelerate fat metabolism, and reduce fatty liver disease in animal models.

"FGF21 is a key molecule to regulate metabolism in the liver," said Wan. "There's research that shows that mice that overexpress FGF21 live 50 percent longer. Now we've shown that it can rescue human PPAR, allowing it to completely regenerate damaged livers in mice. This could provide significant therapeutic benefits for people after transplants or other liver injury."

Other authors included Hui-Xin Liu and Ying Hu at UC Davis, Samuel W. French at Harbor-UCLA Medical Center and Frank J. Gonzalez at the National Cancer Institute.

Researchers at UC Davis have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPARα, which activates liver regeneration. Normally, mouse PPARα is far more active and efficient than the human form, allowing mice to quickly regenerate damaged livers. However, the research shows that protein fibroblast growth factor 21 (FGF21) can boost the regenerative effects of human PPARα. The findings suggest that the molecule could offer significant therapeutic benefits for patients who have had a liver transplant or suffer from liver disease. The study was published in the journal Oncotarget.

"We found that FGF21 is a good rescuing molecule that facilitates liver regeneration and perhaps tissue repair," said Yu-Jui Yvonne Wan, vice chair for research in the Department of Pathology and Laboratory Medicine at UC Davis and senior author on the paper. "Our data suggests that FGF21 could help with liver regeneration, either after removal or after damage caused by alcohol or a virus."

In the study, human and mouse PPARα showed different capacities for liver regeneration after surgery. Even after having two-thirds of their livers removed, normal mice regained their original liver mass within seven to 10 days. By contrast, mice with human PPARα never fully regenerated, even after three months. However, by increasing FGF21, the team boosted human PPARα's ability to regenerate and heal mouse livers.

While mouse PPARα has regenerative advantages over the human version, there is also a downside, as this ability can lead to cancer. Human PPARα does not cause cancer; however, as noted, it cannot match the mouse protein's regenerative capacity. This trade-off provides a number of advantages on the human side. For example, several popular drugs target PPARα to treat high cholesterol and triglycerides.

Still, in the right context, a more active human PPARα could be a great boon for patients with liver conditions. Using FGF21 to boost this regenerative capacity is an important step in that direction.

These results also add another line to FGF21's impressive resume. In addition to boosting human PPARα's regenerative impact on the liver, the protein has been shown to alleviate insulin resistance, accelerate fat metabolism, and reduce fatty liver disease in animal models.

"FGF21 is a key molecule to regulate metabolism in the liver," said Wan. "There's research that shows that mice that overexpress FGF21 live 50 percent longer. Now we've shown that it can rescue human PPAR, allowing it to completely regenerate damaged livers in mice. This could provide significant therapeutic benefits for people after transplants or other liver injury."
-end-
Other authors included Hui-Xin Liu and Ying Hu at UC Davis, Samuel W. French at Harbor-UCLA Medical Center and Frank J. Gonzalez at the National Cancer Institute.

Learn more at http://cancer.ucdavis.edu

University of California - Davis Health System

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...