Substance P accelerates intestinal tissue regeneration after γ‐irradiation–induced damage

Abstract

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 gamma-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.

Substance P stimulates the recovery of bone marrow after the irradiation

“…Each group had at least 20 mice and some mice of each group were sacrificed at the indicated times. Administration of SP was consistent with our previous study (Kang et al, 2009). Briefly, mice in the SP-treated group were given 2 ml of a 100 mM stock solution in 0.1 ml PBS via intraperitoneal (i.p.)…”

“…Five weeks old female C57BL/6 mice (Central Laboratory, Animal Inc., Seoul, Korea) were maintained under standard conditions and were fed standard chow and water ad libitum, as previously described (Kang et al, 2009). The animals were fed for 7 days, and then divided into a SP (Calbiochem, Darmstadt, Germany)-treated group and a vehicle-treated group.…”

“…The protein concentration of each sample was measured using the BCA reagent (Pierce, Rockford, IL), as previously described (Kang et al, 2009). Equal amounts of proteins were fractionated via 7-15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto nitrocellulose membranes.…”

“…SP stimulates the neurokinin 1 receptor (NK-1R) in various cell types. Research by our group and Koon et al revealed that SP regulates the anti-apoptotic response in human colon cells either via inhibition of the apoptotic pathway or activation of the survival pathway (Koon et al, 2007;Kang et al, 2009). These findings suggest that SP is a potential radio-protector and may therefore mitigate the effects of radiation on bone marrow cells and tissue.…”

Long-term comparative study of Substance-P with methylprednisolone on the development of osteoporosis

“…Furthermore, SP also -sue injury, as shown in radio-induced BM and gastro-intestinal (GI) damages (Kang et al, 2009;Kim et al, , 2010An et al, 2011) and spinal cord injury (Jiang et al, 2012(Jiang et al, , 2013. Multifunctional effects of SP in the process of wound healing propose the SP-peptide as a candidate -ease as well as facilitating tissue repair.…”