Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation. / Seidelin, Jakob Benedict; Larsen, Sylvester; Linnemann, Dorte; Vainer, Ben; Coskun, Mehmet; Troelsen, Jesper Thorvald; Nielsen, Ole Haagen.
In: American Journal of Physiology: Gastrointestinal and Liver Physiology, Vol. 308, No. 2, 01.2015, p. G92-G99.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation
AU - Seidelin, Jakob Benedict
AU - Larsen, Sylvester
AU - Linnemann, Dorte
AU - Vainer, Ben
AU - Coskun, Mehmet
AU - Troelsen, Jesper Thorvald
AU - Nielsen, Ole Haagen
N1 - Copyright © 2015 the American Physiological Society.
PY - 2015/1
Y1 - 2015/1
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.
KW - Apoptosis
KW - Cell Line
KW - Cell Movement
KW - Colon
KW - Enzyme Activation
KW - Epithelial Cells
KW - Humans
KW - Inhibitor of Apoptosis Proteins
KW - Intestinal Mucosa
KW - NF-kappa B
KW - Transforming Growth Factor beta1
KW - Ubiquitin-Protein Ligases
KW - Wound Healing
KW - rac1 GTP-Binding Protein
U2 - 10.1152/ajpgi.00089.2014
DO - 10.1152/ajpgi.00089.2014
M3 - Journal article
C2 - 25394657
VL - 308
SP - G92-G99
JO - American Journal of Physiology: Gastrointestinal and Liver Physiology
JF - American Journal of Physiology: Gastrointestinal and Liver Physiology
SN - 0193-1857
IS - 2
ER -
ID: 155984152