Igf2bp1 Is Required for Full Induction of Ptgs2 mRNA in Colonic Mesenchymal Stem Cells in Mice

被引:61
作者
Manieri, Nicholas A. [1 ]
Drylewicz, Monica R. [1 ]
Miyoshi, Hiroyuki [1 ]
Stappenbeck, Thaddeus S. [1 ]
机构
[1] Washington Univ St Louis Sch Med, Dept Pathol & Immunol, St Louis, MO USA
基金
美国国家卫生研究院;
关键词
Cox-2; Imp-1; ZBP1; Colorectal Cancer; Inflammatory Bowel Disease; BINDING PROTEIN; INTESTINAL MYOFIBROBLASTS; EPITHELIAL-CELLS; STROMAL CELLS; CYCLOOXYGENASE-2; EXPRESSION; GROWTH; INJURY; GENE; CARCINOGENESIS;
D O I
10.1053/j.gastro.2012.03.037
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Prostaglandin-endoperoxide synthase (Ptgs)2 is an enzyme involved in prostaglandin production during the response to mucosal damage. Its expression is regulated, in part, by messenger RNA (mRNA)-binding proteins that control the stability of Ptgs2 mRNA. We used a precise system of colonic injury and repair to identify Ptgs2 mRNA-binding proteins. METHODS: We used endoscopy-guided mucosal excision to create focal injury sites in colons of mice. Wound beds from wild-type, Ptgs2(-/-), Ptgs2(+/-), and Myd88(-/-) mice were analyzed at 2-day intervals after injury for aspects of repair and Ptgs2 expression. We used cultured colonic mesenchymal stem cells (cMSCs) that express Ptgs2 to identify and analyze molecules that regulate Ptgs2 expression. RESULTS: Ptgs2(-/-) mice had defects in wound repair, validating the biopsy technique as a system to study the regulation of Ptgs2. Ptgs2(+/-) mice had similar defects in wound healing, so full induction of Ptgs2 is required for wound repair. In wild-type mice, levels of Ptgs2 mRNA increased significantly in the wound bed 2 and 4 days after injury; the highest levels of Ptgs2 were observed in cMSCs. In a functional small hairpin RNA knockdown screen, we identified Igf2bp1, a VICKZ mRNA-binding protein, as a regulator of Ptgs2 expression in cMSCs. Igf2bp1 also interacted physically with Ptgs2 mRNA. Igf2bp1 expression was induced exclusively in wound-bed cMSCs, and full induction of Ptgs2 and Igf2bp1 during repair required Myd88. CONCLUSIONS: We identified Igf2bp1 as a regulator of Ptgs2 mRNA in mice. Igf2bp1 is required for full induction of Ptgs2 mRNA in cMSCs.
引用
收藏
页码:110 / U653
页数:22
相关论文
共 34 条
[1]   Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].
Adachi, O ;
Kawai, T ;
Takeda, K ;
Matsumoto, M ;
Tsutsui, H ;
Sakagami, M ;
Nakanishi, K ;
Akira, S .
IMMUNITY, 1998, 9 (01) :143-150
[2]   AU-rich elements and associated factors: are there unifying principles? [J].
Barreau, C ;
Paillard, L ;
Osborne, HB .
NUCLEIC ACIDS RESEARCH, 2005, 33 (22) :7138-7150
[3]   Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury [J].
Brown, Sarah L. ;
Riehl, Terrence E. ;
Walker, Monica R. ;
Geske, Michael J. ;
Doherty, Jason M. ;
Stenson, William F. ;
Stappenbeck, Thaddeus S. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (01) :258-269
[4]   The 3′-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency [J].
Cok, SJ ;
Morrison, AR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (25) :23179-23185
[5]   ALPHA-SMOOTH MUSCLE ACTIN IS EXPRESSED IN A SUBPOPULATION OF CULTURED AND CLONED FIBROBLASTS AND IS MODULATED BY GAMMA-INTERFERON [J].
DESMOULIERE, A ;
RUBBIABRANDT, L ;
ABDIU, A ;
WALZ, T ;
MACIEIRACOELHO, A ;
GABBIANI, G .
EXPERIMENTAL CELL RESEARCH, 1992, 201 (01) :64-73
[6]   Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement [J].
Dominici, M. ;
Le Blanc, K. ;
Mueller, I. ;
Slaper-Cortenbach, I. ;
Marini, F. C. ;
Krause, D. S. ;
Deans, R. J. ;
Keating, A. ;
Prockop, D. J. ;
Horwitz, E. M. .
CYTOTHERAPY, 2006, 8 (04) :315-317
[7]   Fgf9 signaling regulates small intestinal elongation and mesenchymal development [J].
Geske, Michael J. ;
Zhang, Xiuqin ;
Patel, Khushbu K. ;
Ornitz, David M. ;
Stappenbeck, Thaddeus S. .
DEVELOPMENT, 2008, 135 (17) :2959-2968
[8]   Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice [J].
Hansen, TVO ;
Hammer, NA ;
Nielsen, J ;
Madsen, M ;
Dalbaeck, C ;
Wewer, UM ;
Christiansen, J ;
Nielsen, FC .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (10) :4448-4464
[9]   Imaging cyclooxygenase-2 (Cox-2) gene expression in living animals with a luciferase knock-in reporter gene [J].
Ishikawa, Tomo-O ;
Jain, Naveen K. ;
Taketo, Makoto M. ;
Herschman, Harvey R. .
MOLECULAR IMAGING AND BIOLOGY, 2006, 8 (03) :171-187
[10]   Cox-2 deletion in myeloid and endothelial cells, but not in epithelial cells, exacerbates murine colitis. [J].
Ishikawa, Tomo-o ;
Oshima, Masanobu ;
Herschman, Harvey R. .
CARCINOGENESIS, 2011, 32 (03) :417-426