The effect of hepatocyte growth factor on gut mucosal apoptosis and proliferation, and cellular mediators after severe trauma

Abstract

Background: A severe burn injury is associated with an impairment of gut mucosal integrity and function, which is due to increases in small-bowel epithelial cell apoptosis and decreases in cell proliferation. Hepatocyte growth factor (HGF) was shown to improve regeneration in the liver, mesentery, and skin. The purpose of this study was to determine whether HGF can improve small-bowel homeostasis after injury and the cellular mechanisms by which these changes occur.

Methods: Rats were pair-fed, underwent thermal trauma, and received saline (0.9% NaCl; n = 28) or HGF (200 microg/kg iv every 12 hours, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators, such as caspase-3 and caspase-7, Fas and Fas-ligand, Bcl-2, and Bax. In addition, serum cytokines were determined.

Results: Gut epithelial cell apoptosis was increased in the saline and HGF groups after the thermal injury. Despite an increase in serum tumor necrosis factor-alpha and interleukin-1beta, HGF did not affect small-bowel cell apoptosis, but it improved proliferation at days 1 and 2 after injury, which was associated with increased villous height and cell per villous, compared with saline controls, P < .05. Increased mucosal cell proliferation was associated with increased Bcl-2 in the HGF group, P < .05. HGF had no effect on apoptotic mediators, such as Fas, Fas-L, or caspase-3 and caspase-7.

Conclusions: HGF improves small-bowel morphology after a severe burn by increasing mucosal Bcl-2 and, concomitantly, small-bowel epithelial cell proliferation.