Genomics-Based Paper Published in Journal of Biological Chemistry
A study by Biogen scientists published this week in the Journal of Biological Chemistry demonstrates for the first time that kidney fibrosis, the hallmark of most types of progressive kidney disease, is characterized by elevated levels of macrophage genes. The research also identifies previously overlooked inflammatory events in the kidney that may lead directly to renal failure, and points to possible new strategies for the treatment of chronic inflammatory and fibrotic diseases by targeting the expression of a protein known as alpha-1 integrin.
Fibrosis is pathological scarring that can lead to organ failure and eventual death. Although it is not known what triggers the fibrotic response, kidney fibrosis is characterized by the presence of myofibroblasts, which are cells that produce scar tissue, and also matrix and matrix-remodeling genes. The over-expression of these genes leads to increased matrix accumulation in the kidney.
The Biogen team, led by Philip Gotwals, Ph.D., and Victor Kotelianski, Ph.D., M.D., performed gene expression analysis of kidneys from a mouse model of Alport’s syndrome, a rare genetic disorder, and identified the presence of macrophage genes in addition to the matrix and matrix-remodeling genes. Through immunohistochemical analysis of renal sections, they also demonstrated that macrophages, as well as myofibroblasts, accumulate in the kidney.
Dr. Gotwals, Associate Director of Fibrosis Research, said, “This research demonstrates that gene expression levels in macrophages, which are associated with immune response, are up-regulated in kidney fibrosis. It also shows that there are previously overlooked inflammatory events that occur in the kidney that are associated with the fibrotic process. In addition, it demonstrates that by blocking the protein known as alpha-1 integrin, you can slow both the fibrotic process and the accumulation of macrophages. Equally important, you delay disease progression. This study suggests that the alpha-1 integrin pathway may be critical for the accumulation of cells in the tubular interstitium that may lead directly to renal failure.”
Dr. Kotelianski, Director of Biological Research, said, “This research is an important example of how Biogen is using an integrated biological approach to understand a pathological problem. We are using genetics, genomics and immunopathology to better understand a complicated disease and to define new therapeutic targets. Biogen maintains an active research program in fibrosis, which is one of our key research focus areas.”
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Biogen, Inc., winner of the U.S. National Medal of Technology, is a biopharmaceutical company principally engaged in discovering and developing drugs for human healthcare through genetic engineering. Headquartered in Cambridge, MA, the Company’s revenues are generated from international sales of AVONEX® (Interferon beta-1a) for treatment of relapsing forms of
multiple sclerosis, and from the worldwide sales by licensees of a number of products, including alpha interferon and hepatitis B vaccines and diagnostic products. Biogen’s research and development activities are focused on novel products to treat inflammatory and autoimmune diseases, neurological diseases, cancer, fibrosis and congestive heart failure. The Company maintains active clinical research programs in protein therapeutics, small molecules, genomics and gene therapy. For copies of press releases and additional information about the Company, please consult Biogen’s Homepage on the World Wide Web at http://www.biogen.com