3 research outputs found
Periostin in Inflammatory Bowel Disease (IBD) development and synergistic effects mediated via CCL5
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] Welldocumented,
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. The matricellular protein Periostin
has recently been shown to be involved in IBD [2] (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unpublished data).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 [2].
CCL5, also know as RANTES, is a chemokine shown to be
interacting with the G protein-coupled receptors CCR1, CCR3 and
CCR5 [3]. In a recent study it could be shown that CCR5 expression
correlates with the infiltration of inflammatory cells into the lamina
propria of IBD patients [4].
Periostin is a matricellular protein originally isolated from
osteoblasts and found to be preferentially expressed in the
periosteum [5, 6]. 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 IN INFLAMMATORY BOWEL DISEASE (IBD) DEVELOPMENT AND SYNERGISTIC EFFECTS MEDIATED VIA CCL5
Inflammatory bowel disease (IBD) is characterized by chronic inflammation in any part of
the gastrointestinal tract (Ulcerative colitis and Crohn’s disease) and leads to severe damage
mostly of small and/or large intestines. Periostin is both, an extracellular and a matricellular
protein that involved in formation and functioning of several different organs and
biologically important signaling pathways. The precise role of periostin in IBD is still
unclear, although the impact of protein in the intestinal inflammation has been demonstrated.
CCR5, a seven transmembrane G-coupled receptor, is potentially associated with chronic
inflammation, leading to significant consequences. The mode of action from CCR5 in IBD
may be linked to effects mediated by periostin or act independently. We investigated the
patterns of Periostin and CCR5 expression in tissue samples from wild type and Periostin
knockout DSS and TNBS treated mice employing immunohistochemical staining. The
absence of periostin seems to reduce the amount of the CCR5 expression in animal models of
colitis (DSS and TNBS). The acute colitis was induced by oral DSS and rectal TNBS
administration. An experiment involving live mice and the use of CCL5 5p12 5m and
Maraviroc injections and oral consumption of Maraviroc was carried out and some results
obtained, but further analysis is still ongoing
Expression profile of the matricellular protein periostin in paediatric inflammatory bowel disease
The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear. Here, we investigated periostin in paediatric IBD including its relationship with disease activity, clinical outcomes, genomic variation and expression in the colonic tissue. Plasma periostin was analysed using ELISA in 144 paediatric patients and 38 controls. Plasma levels were assessed against validated disease activity indices in IBD and clinical outcomes. An immuno-fluorescence for periostin and detailed isoform-expression analysis in the colonic tissue was performed in 23 individuals. We integrated a whole-gene based burden metric ‘GenePy’ to assess the impact of variation in POSTN and 23 other genes functionally connected to periostin. We found that plasma periostin levels were significantly increased during remission compared to active Crohn’s disease. The immuno-fluorescence analysis demonstrated enhanced peri-cryptal ring patterns in patients compared to controls, present throughout inflamed, as well as macroscopically non-inflamed colonic tissue. Interestingly, the pattern of isoforms remained unchanged during bowel inflammation compared to healthy controls. In addition to its role during the inflammatory processes in IBD, periostin may have an additional prominent role in mucosal repair. Additional studies will be necessary to understand its role in the pathogenesis, repair and fibrosis in IBD