Periostin in inflammatory bowel disease (IBD) development and synergistic effects mediated via CCL5 and MMP9.

Faculty Development Competitive Research Grant Program 2018-2020

The incidence of IBD is rising all over the world and is affecting 1 in 4000 people in Europe and 1 in 16.000 in Asia. [1] Well-documented, reliable numbers for Kazakhstan are currently not available but observations from local physicians (personal communication) suggest that numbers might be significantly higher than suggested by the literature. As most chronic diseases IBD has an enormous socio-economic impact. It is not only the burden on the healthcare system and individual related to medical cost but also indirect costs like sick-leave, reduced employment options, early mortality and the social stigma of a chronic disease that are adding up [2]. The matricellular protein Periostin has recently been shown to be involved in IBD [3] (and our own unpublished data). In a chemically induced murine model (dextrane sulfate sodium DSS) it mediates intestinal inflammation through the activation of NF-κB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease [3]. Periostin is a matricellular protein originally isolated from osteoblasts and found to be preferentially expressed in the periosteum [4, 5]. Periostin contains an N-terminal secretory signal peptide, followed by a cysteine-rich domain, four internal homologous repeats, and a C-terminal hydrophilic domain. The four internal repeats exhibit homology to the axon guidance protein fasciclin I that is involved in the development of nervous system in invertebrates and were thus named fasciclin domains. Periostin has been shown to be upregulated in a variety of different inflammatory events including IBD [3, 6] and is involved in a variety of signaling pathways including integrin signaling [7, 8]. We and others have generated periostin-deficient mice that are viable [9-11] (and A. Brodarac PhD thesis, 2006). These animals serve as an extremely useful tool to analyze the various functions of Periostin in different settings (disease, regeneration).