生物学奖发现果蝇的8个伤口愈合基因

Biologists at UC San Diego have identified eight genes¹ never before suspected to play a role in wound healing that are called into action near the areas where wounds occur. Their discovery, detailed² this week in the open-access journal PLOS ONE, was made in the laboratory fruit fly Drosophila. But the biologists say many of the same genes that regulate biological processes in the hard exoskeleton（外骨骼）, or cuticle³（角质层，表皮）, of Drosophila also control processes in human skin. That makes them attractive candidates for new kinds of wound-healing drugs or other compounds that could be used to treat skin ailments⁴.

 

"Many of the key molecules⁵ and proteins involved in Drosophila wound healing are involved in mammalian wound healing," says Rachel Patterson, the first author who published the paper with Michelle Juarez and William McGinnis, a professor of biology and interim⁶ dean of the Division of Biological Sciences. "The genetics of Drosophila are not as complicated as mammalian genetics, so it's easier to attribute specific biological functions to individual genes."

 

By puncturing⁷ the cuticle and epidermis⁸ of fruit fly embryos¹⁰ in their experiments, the researchers examined 84 genes that are turned on and 78 that are turned off as the fly embryo⁹ responds to healing. From these 162 genes, they identified eight genes that are expressed at either very low levels or not at all in most cells during development, but are activated¹¹ near the puncture¹² wounds.

 

The researchers were surprised to discover that an immune response begins as soon as the flies' cuticles¹³ and epidermis were punctured¹⁴, releasing antimicrobial peptides and other compounds that prepare the embryo should bacteria or fungi¹⁵ enter the site of injury. The key to their technique was the use of trypsin, a member of a family of enzymes¹⁶ called serine proteases（丝氨酸蛋白酶）, which activates¹⁷ genes involved in wound healing. The next step is to see if these genes play a comparable role in humans.

 

"I think one amazing application of our studies may be to build a better bandage -- containing compounds to promote would healing," said Juarez, a former postdoctoral fellow in McGinnis's lab who is now an assistant medical professor at the City College of New York.

 

"Perhaps our results can be translated to existing human therapies by incorporating specific, regulated series proteases and antimicrobial peptides at the sites of diabetic ulcers¹⁸（溃疡） or skin grafts¹⁹ for more efficient wound healing," said Patterson. She said her team's results might also have application to treating chronic²⁰ skin diseases such as psoriasis, severe dry skin and eczema（湿疹） in which levels of these enzymes are known to be abnormal.

 

Funding for the study was provided by the National Institutes of Health (GM077197 and HD28315), a Developmental Biology of Neural²¹ Diseases Training grant, the Ray Thomas Edwards Fellowship and the family of Herbert Stern.

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