What do a paper cut, skinned knee, and a surgical incision have in common? They each trigger a wound healing response that uses the same mechanism the body uses to remove toxins. Surprisingly, the process depends on an antioxidant important in bone — vitamin D.
During his NIEHS Distinguished Lecture seminar Feb. 7, Ronald Evans, Ph.D., a researcher at the Salk Institute for Biological Studies in La Jolla, California, discussed how a therapy using a synthetic version of vitamin D affected wound healing and might prevent scarring of the liver, which is known as fibrosis.
Vitamin D stops wound healing
Evans said that as omnivores, humans eat just about everything, and most of it is not nutritious. The body sorts out the good stuff and gets rid of the toxins, which are known as xenobiotics. When Evans and his research group were studying how the liver detoxifies the body, they stumbled across a novel mechanism that strengthens the liver against certain types of xenobiotic toxins.
Although the liver has virtually no vitamin D receptors (VDRs), which are molecules that bind with vitamin D to make it work, the organ does contain cells known as hepatic stellate cells (HSCs). Evans’ team found that these cells, which make up 2 to 3 percent of liver tissue, do have VDRs. These cells are activated when the liver is mechanically or chemically injured.
The importance of VDRs becomes clear when they are removed. "When we knocked out VDRs in the liver or pancreas of a particular mice strain, the animals exhibited spontaneous liver and pancreas fibrosis," Evans said. "Since proinflammatory repair proteins are a major part of wound healing, we think VDRs are acting as a brake on the inflammation associated with healing [so that it does not go too far]. Without that brake, you get a fibrotic and cirrhotic liver."
Synthetic vitamin D makes a difference
Evans said that scientists have tried to take advantage of vitamin D’s ability to control the wound healing process in patients with liver cancer. By giving these patients vitamin D, they hoped to calm down the healing and inflammation pathway so that it did not lead to fibrosis.
Those trials failed, and Evans theorizes that is because they used natural vitamin D paired with VDRs. In his lab, a synthetic form of vitamin D called calipotriol is being used, because it does not break down.
His group has completed a successful clinical trial using this treatment. He is cautiously optimistic the approach will lead to therapies that make a difference to patients.
Michelle Heacock, Ph.D., a health scientist administrator in the NIEHS Extramural Research and Training Division, hosted the seminar. "His research takes a molecular approach to develop strategies to mitigate the health effects," she said of Evans’ work.