RETINOIC ACID PLAYS KEY ROLE IN SUN DAMAGE TO SKIN
Gary Fisher and John Voorhees |
How does ultraviolet radiation cause so much damage to human
skin? University of Michigan scientists have discovered an important
new piece of the puzzle, which they describe in an article published
in the March 29, 1999 issue of Nature Medicine.
“We found that ultraviolet irradiation blocks the ability
of skin cells to recognize and respond to an essential nutrient
called retinoic acid, which skin cells make from vitamin A or
retinol,” said John J. Voorhees, M.D., the Duncan and Ella
Poth Distinguished Professor of Dermatology in the U-M Medical
School. “The inability to respond to retinoic acid triggers
a cascade of biochemical changes that upsets the normal balance
between healthy and dying skin cells. In essence, ultraviolet
radiation causes a functional vitamin A deficiency in human
skin.
“We also found that pretreating skin with retinoic acid—the
active form of vitamin A— before ultraviolet radiation
exposure limits the extent of the harmful biochemical changes.”
According to Gary J. Fisher, Ph.D., associate professor of
dermatology and the study’s co-author, ultraviolet radiation
causes a major loss of retinoic acid receptors found in human
skin cells. “Retinoic acid receptors are the molecular
mediators of the biological actions of vitamin A. When retinoic
acid receptors are lost, it is as if the skin has no vitamin
A,” Fisher explained.
“This is a bad situation because vitamin A is required
for normal skin development and function. Retinoic acid receptors,
when activated by retinoic acid, transfer genetic instructions
from DNA to the cell’s protein-producing factory telling
it to assemble proteins needed for skin cell function.
“Eight hours after skin was exposed to ultraviolet radiation
in our study, amounts of retinoic acid receptor messenger RNA
and protein were as much as 70 percent lower than control levels.
They remained below normal levels for more than 24 hours after
exposure,” Fisher said.
When the biochemical retinoic acid receptor pathway is shut
down, other dangerous skin changes—which also occur in
response to ultraviolet radiation exposure—can proceed
unchecked. “In this process, ultraviolet radiation activates
a protein complex called AP-1, which causes production of large
amounts of enzymes called matrix metalloproteinases or MMPs,”
Voorhees explained. “These MMPs break apart and degrade
collagen and elastin, the major structural materials in skin.
Although the broken-down collagen and elastin are replaced,
the repair process is imperfect. This imperfect repair results
in a tiny defect in the skin. With repeated ultraviolet radiation
exposures, the defect grows and eventually results in the wrinkled
appearance of sun-damaged skin. In addition, the biochemical
changes associated with activation of AP-1 and production of
MMPs promote skin cancer.”
Although additional research will be needed to completely understand
the complex relationship between the retinoic acid receptor
pathway and the pathway responsible for producing enzymes that
destroy skin collagen, Voorhees and his colleagues believe the
two may exist in a state of dynamic balance. This dynamic balance
may be necessary to maintain healthy skin.
In addition to Voorhees and Fisher, co-investigators on the
U-M study were ZengQuan Wang, Mohamed Boudjelal and Sewon Kang,
all from the Department of Dermatology. The research was funded
by the Babcock Endowment for Dermatological Research, the Dermatology
Foundation and the Johnson & Johnson Corporation.
You may reach Gary Fisher at gjfisher@umich.edu
You may reach John Voorhees at voorhees@umich.edu
 
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