Making mouse psoriasis relevant

The red scaly patches that are the hallmark of psoriasis can be unsightly and quite irritating. Although psoriasis is a common skin condition that results from an overactive immune system, researchers still do not understand its exact causes. Treatments exist, but none is a cure. Moreover, the most potent therapies have the most serious side effects, and psoriasis can become resistant to treatments.

Scientists are researching new signaling pathways in psoriasis to find new drug targets. A research group at Case Western Reserve University led by Nicole Ward and Mark Chance recently reported in Molecular & Cellular Proteomics four proteins that are promising.

The researchers harvested skin samples from genetically modified mice that develop a skin condition similar to psoriasis. Using proteomics analysis and gene-expression measurement techniques, the researchers discovered and validated four proteins that were significantly higher in the psoriasis mice: SerpinB1; kallikrein-related peptidase 6, or KLK6; Cystatin A; and solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator) member 5, or Slc25a5.

The investigators next took skin samples from psoriasis patients and measured the expression levels of these proteins along with Ras-related protein Rab18, a protein that they found did not change in the psoriasis mice. Consistent with the mice, the psoriasis patient skin samples had higher expression of the four proteins, while Rab18 was unchanged, demonstrating that these proteins are relevant in humans and that the mouse is a good model for human psoriasis.

Ward says of the study’s findings: “When we talk about translational biology, this is what we’re talking about: going from the bench in the lab — the mouse model, identifying something new, then going back to the patient and validating that what we found in the research lab actually matters to patients.”

Learn how the psoriasis mouse came to be in this month’s installment of the “Generations” series

The investigators now are defining the roles of their proteins in psoriasis. Ward admits that she is not sure if the proteins can be viable drug targets but “maybe something downstream in terms of what they affect or how they change inflammation” will be, she says.

“This is just the first step,” Ward continues. “Now that we have a list of proteins that we know may be important, we’re going to try to study what they’re actually doing at the biological level.”

Maggie Kuo Maggie Kuo was an intern at ASBMB Today when she wrote this story. Today she is a writer at the American Physiological Society. She earned her Ph.D. in biomedical engineering at Johns Hopkins University.