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Autotaxin (ATX or ENPP2) is a secreted lysophospholipase D that produces lysophosphatidic acid (LPA), a pleiotropic lipid mediator acting on specific GPCRs. ATX and LPA have been implicated in key (patho)physiologic processes, including embryonic development, lymphocyte homing, inflammation, and cancer progression. Using LPA receptor knockout mice, we previously uncovered a role for LPA signaling in promoting colitis and colorectal cancer. Here, we examined the role of ATX in experimental colitis through inducible deletion of Enpp2 in adult mice. ATX expression was increased upon induction of colitis, whereas ATX deletion reduced the severity of inflammation in both acute and chronic colitis, accompanied by transient weight loss. ATX expression in lymphocytes was strongly reduced in Rag1 and μMT mice, suggesting B cells as a major ATX-producing source, which was validated by immunofluorescence and biochemical analyses. ATX secretion by B cells from control, but not Enpp2 knockout, mice led to ERK activation in colorectal cancer cells and promoted T cell migration. We conclude that ATX deletion suppresses experimental colitis and that B cells are a major source of ATX in the colon. Our study suggests that pharmacological inhibition of ATX could be a therapeutic strategy in colitis.-Lin, S., Haque, A., Raeman, R., Guo, L., He, P., Denning, T. L., El-Rayes, B., Moolenaar, W. H., Yun, C. C. Autotaxin determines colitis severity in mice and is secreted by B cells in the colon.
This article was published in the following journal.
Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Autotaxin-lysophosphatidic acid (ATX-LPA) axis is closely associated with several inflammation-related diseases. In the colonic mucosa of patients with chronic ulcerative colitis (UC), the expression ...
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A subtype of MICROSCOPIC COLITIS, characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. Microscopic examination of biopsy samples taken from the COLON show larger-than-normal band of subepithelial COLLAGEN.
A subtype of MICROSCOPIC COLITIS, characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. Microscopic examination of biopsy samples taken from the COLON show infiltration of LYMPHOCYTES in the superficial EPITHELIUM and the underlying connective tissue (lamina propria).
The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.
Cell surface proteins that bind pancreatic hormones with high affinity and trigger intracellular changes which influence the behavior of cells. These include receptors for glucagon (secreted by alpha cells), insulin (secreted by beta cells), somatostatin (secreted by delta cells), and pancreatic peptide (secreted by PP cells). Some of these hormones and receptors also support neurotransmission.
Inflammation of the COLON due to colonic ISCHEMIA resulting from alterations in systemic circulation or local vasculature.
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