Premium
Substance P accelerates intestinal tissue regeneration after γ‐irradiation–induced damage
Author(s) -
Kang MiHyun,
Kim DoYeon,
Yi Jae Youn,
Son Youngsook
Publication year - 2009
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2009.00456.x
Subject(s) - cell growth , protein kinase b , apoptosis , microbiology and biotechnology , mapk/erk pathway , tunel assay , cell , biology , regeneration (biology) , chemistry , signal transduction , biochemistry
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.