Cellular inhibitor of apoptosis protein 2 (cIAP2) controls human colonic epithelial restitution, migration and Rac1 activation.

JB Seidelin, Sylvester Larsen, D Linnemann, Ben Vainer, Mehmet Coskun, Jesper Thorvald Troelsen, Ole Hagen Nielsen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in non-epithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24 and 48 hours. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 hours (P < 0.05) and returned to normal after re-epithelialization and correlated with the inflammatory reaction in the experimental wounds (P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction (P < 0.01). Knock down of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration (P < 0.005). cIAP2 over-expression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor β1 enhanced the expression of cIAP2, but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1 and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing.
    OriginalsprogEngelsk
    TidsskriftAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
    Vol/bind308
    Udgave nummer2
    ISSN0193-1857
    DOI
    StatusUdgivet - 2015

    Citer dette

    @article{f5a96699edaf444ca106b258f38ec550,
    title = "Cellular inhibitor of apoptosis protein 2 (cIAP2) controls human colonic epithelial restitution, migration and Rac1 activation.",
    abstract = "Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in nonepithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 h (P < 0.05), returned to normal after reepithelialization, and correlated with the inflammatory reaction in the experimental wounds (P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction (P < 0.01). Knockdown of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration (P < 0.005). cIAP2 overexpression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor-β1 enhanced the expression of cIAP2 but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing",
    author = "JB Seidelin and Sylvester Larsen and D Linnemann and Ben Vainer and Mehmet Coskun and Troelsen, {Jesper Thorvald} and {Hagen Nielsen}, Ole",
    year = "2015",
    doi = "10.1152/ajpgi.00089.2014",
    language = "English",
    volume = "308",
    journal = "American Journal of Physiology: Gastrointestinal and Liver Physiology",
    issn = "0193-1857",
    publisher = "American Physiological Society",
    number = "2",

    }

    Cellular inhibitor of apoptosis protein 2 (cIAP2) controls human colonic epithelial restitution, migration and Rac1 activation. / Seidelin, JB; Larsen, Sylvester; Linnemann, D; Vainer, Ben; Coskun, Mehmet; Troelsen, Jesper Thorvald; Hagen Nielsen, Ole .

    I: American Journal of Physiology: Gastrointestinal and Liver Physiology, Bind 308, Nr. 2, 2015.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Cellular inhibitor of apoptosis protein 2 (cIAP2) controls human colonic epithelial restitution, migration and Rac1 activation.

    AU - Seidelin, JB

    AU - Larsen, Sylvester

    AU - Linnemann, D

    AU - Vainer, Ben

    AU - Coskun, Mehmet

    AU - Troelsen, Jesper Thorvald

    AU - Hagen Nielsen, Ole

    PY - 2015

    Y1 - 2015

    N2 - Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in nonepithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 h (P < 0.05), returned to normal after reepithelialization, and correlated with the inflammatory reaction in the experimental wounds (P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction (P < 0.01). Knockdown of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration (P < 0.005). cIAP2 overexpression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor-β1 enhanced the expression of cIAP2 but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing

    AB - Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in nonepithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 h (P < 0.05), returned to normal after reepithelialization, and correlated with the inflammatory reaction in the experimental wounds (P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction (P < 0.01). Knockdown of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration (P < 0.005). cIAP2 overexpression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor-β1 enhanced the expression of cIAP2 but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing

    U2 - 10.1152/ajpgi.00089.2014

    DO - 10.1152/ajpgi.00089.2014

    M3 - Journal article

    VL - 308

    JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

    JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

    SN - 0193-1857

    IS - 2

    ER -