Basic Fibroblast Growth Factor Suppresses Radiation-Induced Apoptosis and TP53 Pathway in Rat Small Intestine

Abstract

The effect of basic fibroblast growth factor (bFGF) was studied in radiation-induced apoptosis in rat jejunal crypt cells. Six-week-old male Wistar rats were administered 4 mg/kg bFGF intraperitoneally 25 h before receiving 8 Gy whole-body X rays. The jejunum was removed for analysis from time 0 to 120 h after irradiation. Villus length in control rats declined steadily until 72 h, while in bFGF-treated rats the villi were longer than in the controls until 48 h. Crypt lengths were similar to villi. bFGF treatment increased Ki-67-positive cells in the jejunal crypt at 0, 24 and 48 h. The treatment with bFGF reduced the number of apoptotic cells per jejunal crypt to 23% and 10% of the control values at 3 and 6 h, respectively, and increased numbers of mitotic cells significantly at 48 and 72 h. bFGF decreased the levels of TP53, CDKN1A, Puma and Cleaved caspase 3 at 3 h as detected by Western blot analyses. Our results suggest that bFGF protected against acute radiation-induced injury by suppressing the crypt apoptotic cells including the stem cells and promoted crypt cell proliferation. The inhibition of apoptosis thus might be related to suppression of the TP53 pathway.

Radiotherapy and wound healing: Principles, management and prospects (Review)

“…however, it is beyond the scope of this article to explore this background knowledge. subsequently, the listed growth factors are the key factors in wound healing (45,46).…”

Response of Crypt Paneth Cells in the Small Intestine following Total-Body γ-Irradiation

“…As we stated above, we consider the observed Paneth cell activation as a consequent compensatory response to complex alterations in intestinal mucosa that are temporally and functionally associated with further development of symptoms of the acute radiation illness. Therefore, we would expect a shorter time point of Paneth cell activation with increasing irradiation dose> lOGy and vice versa (2,27).…”

“…Recent observations indicate that irradiation with doses of -9 Gy does not, per se, cause collapse of crypt/villi structures (2). Taking into consideration the concept of dynamic response of entorocytes to irradiation discussed above, we assumed that enteritis associated with 'the development of acute radiation syndrome reported in this and previous communications is not likely due to the early apoptosis of the proliferating crypt cells, but rather due to irradiation-induced temporal arrest of epithelial cell proliferation, and cell renewal along the cryp/villus axis (20)(21)27). This assumption was corroborated by the appearance of bacteria in crypt lumens of irradiated intestine (Fig.…”

“…Indeed , the irradiation response of the crypt proliferating cells is relatively fast across a wide range of radiation doses. Subsequently, they are subjected to apoptotic elimination from the crypt cell population (2,27). The completely differentiated epithelial cells constitute the apex of villi.…”

Application of human bone marrow-derived mesenchymal stem cells in the treatment of radiation-induced Gastrointestinal syndrome

“…Currently, there are no approved medical countermeasures to alleviate GI syndrome. Several studies have shown that cytokines such as interleukin 11 (IL-11), granulocyte colony-stimulating factor (G-CSF) and basic fibroblast growth factor (b-FGF) could inhibit apoptosis of intestinal epithelial cells and impair radiation-induced intestinal damage [8,9]. However, cytokine treatment is not effective against higher doses of radiation-induced tissue injury.…”