Therapeutic efficacy of a mutant of keratinocyte growth factor-2 on trinitrobenzene sulfonic acid-induced rat model of Crohn’s disease

摘要

Background: Keratinocyte growth factor-2 (KGF-2) has been testified to be a multifunctional growth factor, which can stimulate the regeneration and reconstruction of epidermis, corium and mucosa. Its effect on Crohn’s disease has hitherto not been evaluated. Here, we investigated the preventive and therapeutic actions of STEA, a mutant of human KGF-2 with high activity, on trinitrobenzene sulfonic acid (TNBS)-induced rat model of Crohn’s disease. Methods: Rats with TNBS-induced colitis were treated with STEA and clinical scores were evaluated. Body weight, mortality, macroscopic and microscopic damage of the colonic tissue were examined. The levels of inflammatory cytokines in serum were detected by ELISA, the T cell subpopulations and the cell cycle of intestinal epithelial cells were analyzed by flow cytometry. Results: Both preventive and therapeutic administration of STEA significantly ameliorated body weight loss, diarrhea, and intestinal inflammation, reduced the high mortality and histopathologic damage of rats with TNBS-induced colitis. The serum level of inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ and IL-6 were markedly decreased in colitis rats treated with STEA. The CD4+ and CD8+ T lymphocytes in peripheral blood were reduced with STEA administration at early stage of colitis. In addition, STEA treatment could promote the growth of intestinal epithelial cells by increasing the cell proportion in S phase of cell cycle and inhibiting cell apoptosis. Conclusions: Both preventive and therapeutic administration of STEA could ameliorate the colonic damages in rats with TNBS-induced colitis. STEA might be a promising option for the treatment of Crohn’s disease.