CD44v6 expression in inflammatory bowel disease is associated with activity detected by endoscopy and pathological features

Camacho, Francisca I.; Muñoz, Concepción; Sánchez-Verde, Lydia; Sáez, Antonia; Alcántara, M; Rodríguez, R.

doi:10.1046/j.1365-2559.1999.00712.x

Cited by 12 publications

(8 citation statements)

References 21 publications

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“…Further analysis revealed binding of GM35 to a v6-containing variant of CD44 (CD44v6). The expression of CD44v6 in epithelial cells reported in the current work is supported by previous studies which report that alternative splicing of CD44 is mediated by tissue-specific factors with certain variant exon products being differentially expressed (or at least predominantly found) on defined tissues such as epithelium (45–48). Further, the expression of the GM35 ligand in T84 and HT29 cells but not in other epithelial cell lines is in keeping with its binding to CD44v6 as it has been reported that this large, heavily glycosylated protein is expressed in these epithelial cell lines but not in Caco2 colon cells (37).…”

Section: Discussionsupporting

confidence: 89%

Neutrophil Migration across Intestinal Epithelium: Evidence for a Role of CD44 in Regulating Detachment of Migrating Cells from the Luminal Surface

Brazil

Lee

Kolegraff

et al. 2010

The Journal of Immunology

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Summary The migration of polymorphonuclear leukocytes (PMN) across the intestinal epithelium is a histopathological hallmark of many mucosal inflammatory diseases including inflammatory bowel disease (IBD). The terminal transmigration step is the detachment of PMN from the apical surface of the epithelium and their subsequent release into the intestinal lumen. The current study sought to identify epithelial proteins involved in the regulation of PMN migration across intestinal epithelium at the stage where PMN reach the apical epithelial surface. A panel of antibodies reactive with IFNγ-stimulated T84 intestinal epithelial cells was generated. Screening efforts identified one mAb, GM35, which prevented PMN detachment from the apical epithelial surface. Microsequencing studies identified the GM35 antigen as human CD44. Transfection studies confirmed this result by demonstrating the loss of the functional activity of the GM35 mAb following attenuation of epithelial CD44 protein expression. Immunoblotting and immunofluoresence revealed the GM35 antigen to be an apically expressed v6 variant-exon containing form of CD44 (CD44v6). ELISA analysis demonstrated the release of soluble CD44v6 by T84 cells during PMN transepithelial migration (TEM). In addition, the observed release of CD44v6 was blocked by GM35 treatment supporting a connection between CD44v6 release and PMN detachment. Increased expression of CD44v6 and the GM35 antigen was detected in inflamed ulcerative colitis tissue. This study demonstrates for the first time that epithelial expressed CD44v6 plays a role in PMN clearance during inflammatory episodes through regulation of the terminal detachment of PMNs from the apical epithelial surface into the lumen of the intestine.

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Section: Discussionsupporting

confidence: 89%

Neutrophil Migration across Intestinal Epithelium: Evidence for a Role of CD44 in Regulating Detachment of Migrating Cells from the Luminal Surface

Brazil

Lee

Kolegraff

et al. 2010

The Journal of Immunology

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“…Similar colocalization of sLe a and CD44v6 has been reported in inflamed cervical cells and IECs (7,20). The importance of CD44v6 as a marker of epithelial stress is further highlighted by studies showing that CD44v6 expression is restricted to inflamed or squamous epithelia (21,22), and that epithelial CD44v6 expression strongly associates with disease activity in ulcerative colitis (23,24).…”

Section: Discussionsupporting

confidence: 64%

Targeting epithelium-expressed sialyl Lewis glycans improves colonic mucosal wound healing and protects against colitis

Kelm¹,

Quirós²,

Azcutia³

et al. 2020

JCI Insight

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“…In an inflammatory bowel disease (IBD) model, expression of CD44v7 is crucial for colonic inflammation ( 210 , 211 ). Furthermore, CD44v6 expression is associated with IBD severity in patients ( 212 – 214 ). Extensive HA matrix accumulates in bleomycin-induced lung fibrosis in CD44-null mice with persistent lung inflammation, extended chemokine production, impaired clearance of apoptotic lymphocytes, and death ( 215 ).…”

Section: Interaction Of Cd44 and Rhamm With Hamentioning

confidence: 99%

Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer

et al. 2015

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The glycosaminoglycan hyaluronan (HA), a major component of extracellular matrices, and cell surface receptors of HA have been proposed to have pivotal roles in cell proliferation, migration, and invasion, which are necessary for inflammation and cancer progression. CD44 and receptor for HA-mediated motility (RHAMM) are the two main HA-receptors whose biological functions in human and murine inflammations and tumor cells have been investigated comprehensively. HA was initially considered to be only an inert component of connective tissues, but is now known as a “dynamic” molecule with a constant turnover in many tissues through rapid metabolism that involves HA molecules of various sizes: high molecular weight HA (HMW HA), low molecular weight HA, and oligosaccharides. The intracellular signaling pathways initiated by HA interactions with CD44 and RHAMM that lead to inflammatory and tumorigenic responses are complex. Interestingly, these molecules have dual functions in inflammations and tumorigenesis. For example, the presence of CD44 is involved in initiation of arthritis, while the absence of CD44 by genetic deletion in an arthritis mouse model increases rather than decreases disease severity. Similar dual functions of CD44 exist in initiation and progression of cancer. RHAMM overexpression is most commonly linked to cancer progression, whereas loss of RHAMM is associated with malignant peripheral nerve sheath tumor growth. HA may similarly perform dual functions. An abundance of HMW HA can promote malignant cell proliferation and development of cancer, whereas antagonists to HA-CD44 signaling inhibit tumor cell growth in vitro and in vivo by interfering with HMW HA-CD44 interaction. This review describes the roles of HA interactions with CD44 and RHAMM in inflammatory responses and tumor development/progression, and how therapeutic strategies that block these key inflammatory/tumorigenic processes may be developed in rodent and human diseases.

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CD44v6 expression in inflammatory bowel disease is associated with activity detected by endoscopy and pathological features

Cited by 12 publications

References 21 publications

Neutrophil Migration across Intestinal Epithelium: Evidence for a Role of CD44 in Regulating Detachment of Migrating Cells from the Luminal Surface

Neutrophil Migration across Intestinal Epithelium: Evidence for a Role of CD44 in Regulating Detachment of Migrating Cells from the Luminal Surface

Targeting epithelium-expressed sialyl Lewis glycans improves colonic mucosal wound healing and protects against colitis

Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer

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