*Equal contribution as corresponding authors.
Substance P accelerates intestinal tissue regeneration after γ-irradiation–induced damage
Article first published online: 13 MAR 2009
© 2009 by the Wound Healing Society
Wound Repair and Regeneration
Volume 17, Issue 2, pages 216–223, March/April 2009
How to Cite
Kang, M.-H., Kim, D.-Y., Yi, J. Y. and Son, Y. (2009), Substance P accelerates intestinal tissue regeneration after γ-irradiation–induced damage. Wound Repair and Regeneration, 17: 216–223. doi: 10.1111/j.1524-475X.2009.00456.x
- Issue published online: 13 MAR 2009
- Article first published online: 13 MAR 2009
- Manuscript received: May 20, 2008Accepted in final form: October 12, 2008
Radiation therapy causes varying degrees of damage to biological systems. Many groups are investigating the mechanism underlying radiation-induced cellular damage but there are limited therapeutic solutions for affected patients. Recent studies show that substance P (SP) participates in cell proliferation. In the present study, we characterized the mechanism underlying SP-induced cellular signaling in radiation-induced damage of the intestine. Exposure of Caco-2 cells to SP increases cell proliferation and Erk phosphorylation in a time- and dose-dependent manner. The proliferation of cells exposed to γ-irradiation is also stimulated by exposure to SP, a phenomenon that may result from inhibition of apoptosis because SP activates Akt and inhibits the cleavage of caspase-3. The effect of SP on cell proliferation and protection was confirmed by investigations in mice. Proliferating cell nuclear antigen staining shows that cell proliferation in radiation-damaged mouse intestine increases significantly upon exposure to SP. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end labeling assay reveals fewer cells stained in SP-treated mice compared with untreated controls. These findings show the potential for SP-induced acceleration of intestinal wound healing and reveal that the mechanism underlying this process involves activation of Erk and Akt and inhibition of caspase-3 cleavage.