MAdCAM-1 may be a potential therapic target in inflammatory bowel disease
MAdCAM-1 belongs to the immunoglobulin (Ig) superfamily, human MAdCAM
-1 contains two IgSF domains, a transmembrane domain and a 43-residue
cytoplasmic domain. The Ig domains are crucial for binding to ¦Á4¦Â7,
whereas the appropriately O-glycosylated mucin-like structures bind L-
selectin [1,2]. MAdCAM-1 is a cell adhesion molecule that is
constitutively expressed on the high endothelium venules of intestinal
propria, and guides the specific homing of lymphocytes into mucosal
tissues. The proportion of venular endothelium within lamina propria that
expresses MAdCAM-1 is increased at foci associated with inflammatory bowel
disease (IBD), but it is not detected in the majority of normal or
inflamed extra-intestinal tissues, including those with mucosal surfaces
. Recent studies indicates that the up-regulation of MAdCAM-1 on
mucosal have some critical impact on the activity and relapse of IBD.
IBD has traditionally been classified into two subtypes, namely,
ulcerative colitis (UC) and Crohn's disease (CD). Although there are
differents in the underlying cause, both UC and CD are associated with a
massive influx of immune cells into the gut. Up-regulation of
proinflammatory cytokines in IBD leads to increased expression of vascular
adhesion molecules, resulting in a sustained influx of inflammatory cells.
Some of these cells traffic in a gut-tropic manner in response to
increased levels of MAdCAM-1 on mucosal vessels, which promotes
recruitment to the gut lamina propria in IBD . It has been found that
expression of MAdCAM-1 increases with inflammation, especially chronic
inflammation . The crucial role of MAdCAM-1 in IBD makes it an
interesting target for drug development, pioneering studies with
antiadhesion strategies has been clearly shown that the chronic
inflammation was significantly attenuated after treating with anti-¦Á4¦Â7-
integrin monoclonal antibody, MLN-02, formerly LDP-02. Administration of
this antibody markedly improved the clinical and histological scores in
the IBD .
It is reasonable to hypothesize that MAdCAM is probable a determinant
of the development of inflammatory bowel disease, it may be a potential
therapic target in inflammatory bowel disease. Therefore, we can direct
against regulation of the coagulation competence with MAdCAM as one of the
primary target. Recombinant adeno-associated viral (rAAV) vectors are
selected as anti-MAdCAM gene vector. Recombinant adeno-associated viral
vectors have gained attention as a potentially alternative to the more
commonly used retroviral vectors. In our opinion, the adeno-associated
viral human anti-MAdCAM gene seems to hold interesting future prospects
for the treatment of IBD by the suitable injection of vein.
Yiyi Sun1, Zhihe Zang1, Xiaohong Xu1, Zhonglin Zhang1, Ling Zhong1,
Wang Zan1, Yan Zhao1, Lin Sun2*
1.Chengdu Medical College, Chengdu 610083, Sichuan Province, China
2.West China Hospital, Sichuan University, Chengdu 610041, Sichuan
Corresponding Author: Lin Sun, West China Hospital, Sichuan
University, Chengdu 610041, Sichuan Province, China.
Conflict of interest
We declare that we have no conflict of interest.
 Tan K, Casasnovas JM, Liu JH. The structure of immunoglobulin
superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important
for integrin recognition. Structure 1998; 6:793-801.
 Salmi M, Jalkanen S. Molecules controlling lymphocyte migration
to the gut. Gut 1999; 45:148-153.
 Briskin M, Winsor-Hines D, Shyjan A. Human mucosal addressin cell
adhesion molecule-1 is preferentially expressed in intestinal tract and
associated lymphoid tissue. Am J Pathol 1997; 151:97-110.
 Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its role in
the pathogenesis of IBD. Inflamma Bowel Dis 2008; 14:1298-1312.
 Briskin M, Winsor-Hines D, Shyjan A, et al. Human mucosal
addressin cell adhesion molecule-1 is preferentially expressed in
intestinal tract and associated lymphoid tissue. Am J Pathol. 1997; 151:97
 Van Assche G, Rutgeerts P. Physiological basis for novel drug
therapies used to treat the inflammatory bowel diseases. I. Immunology and
therapeutic potential of antiadhesion molecule therapy in inflammatory
bowel disease. Am J Physiol Gastrointest Liver Physiol 2005; 288:G169-174.
Competing interests: No competing interests