Several scientists at Case Western Reserve have confirmed increased presence of the Serpinb3b, KLK6, Stefin A1 and Slc25a5 proteins in human lesional psoriasis skin tissue, and human lesional psoriasis skin cells compared to healthy control skin tissue and skin cells. This is instrumental in identifying the roots of this condition, narrowing the search down to four proteins which appear to be most likely to contribute to this illness.
The Illness
The underlying cause of psoriasis has always been a mystery, but these findings, published in this month' Molecular & Cellular Proteomics, advance our understanding how psoriasis develops, with the hope of developing a treatment. “Psoriasis affects 2 to 3 percent of the population worldwide," said senior author Nicole L. Ward, PhD, associate professor of dermatology and neurosciences, Case Western Reserve University School of Medicine. “The underlying cause of psoriasis remains unknown, and the specific signals that trigger disease onset are still being investigated. There currently is no cure."
Psoriasis is an autoimmune skin disease characterized by well-demarcated areas of red, raised and scaly skin next to areas of normal-appearing skin, it' an inflammatory skin condition affecting 125 million people around the world. Ward' lab is focused on studying the pathogenesis of the disease and any related issues that may arise. Her group is actively working to identify new molecules key to the disease process that could become potential drug targets.
The Culprits
Ward and her team began narrowing down the pool of 50,000 proteins in the human body, and made a list of about 1,280 potential culprits that are differentially regulated in the condition. They then focused on five proteins that stood out either because of their high prevalence in human psoriasis or their prominence in other studies relating to human psoriasis tissue. Using skin tissue samples from her well-established psoriasis transgenic mouse model, called the KC-Tie2 mouse, Ward and her team compared it to skin tissue samples of normal mice.
To ensure that the proteins identified in the mouse were relevant to human psoriasis, the team then examined human psoriasis skin cells, known as keratinocytes, and human psoriasis skin tissue samples to confirm the increased presence of these proteins in human disease. In the skin of the psoriasis mice, investigators first identified increases in stefin A1 (342.4-fold increased; called cystatin A in humans); slc25a5 (46.2-fold increased); serpinb3b (35.6-fold increased; called serpinB1 in humans) and KLK6 (4.7-fold increased). The team found no increases of the Rab18 protein in skin tissue of the mice, and so ruled it out as a psoriasis-generating culprit. Following this discovery, the presence of the proteins was confirmed in human lesional psoriasis skin tissue, and human lesional psoriasis skin cells and compared to healthy control skin tissue and skin cells.
The Results
“We were interested in looking for the increased presence of these proteins, not just in the psoriasis-like skin inflammation of the mouse, but more importantly, we needed to know how the increased presence of these proteins translated to human psoriasis," Ward said. “So we took the information we discovered in the mouse model and went back to the patients and confirmed the increase in these proteins in their lesional psoriasis skin tissue. We are really focused on, and enthusiastic about, our ability to perform successfully translational bench-to bedside-and-back-again psoriasis research here at CWRU School of Medicine Department of Dermatology and the Murdough Family Center for Psoriasis at University Hospitals Case Medical Center. It' what we excel at and what we love to do."
Determining the increased presence of these proteins is just step on the road to helping patients with psoriasis. Ward and her team need to determine the individual contributions of each protein to the condition, which will help provide information on which areas treatment should focus on. Identifying these proteins can help provide a better understand on how these proteins contribute to skin inflammation. “We are always looking for novel targets or new insight into disease progression, remission or susceptibility," Ward said. “It' all about the patients. Even though what we are doing at the bench seems focused on mouse, the ultimate goal is to improve patient care and quality of life for patients."
Products of Interest |
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KLK6 Products |
| Product Name | Catalog No. | Specificity | Applications |
| KLK6 antibody | 70R-2466 | Human | WB |
| KLK6 antibody | 70R-14304 | Human | IHC-P, WB |
| KLK6 blocking peptide | 33R-4416 | Blocks 70R-2466 binding | IHC, WB |
SERPINB3 Products
Stefin A Products
| Product Name | Catalog No. | Specificity | Applications |
| SERPINB3 antibody | 10R-5744 | Human, Dog, Rat, Monkey | WB |
| SERPINB3 protein | 80R-4230 | - | Control, SDS-PAGE |
| Product Name | Catalog No. | Specificity | Applications |
| Stefin A antibody | 70R-30757 | Rabbit | ELISA, IF, IHC, WB |