Protective role of keratinocyte growth factor 2 on dextran sodium sulfate induced murine colitis and intestinal mucosal barrier / 复旦学报（医学版）

ABSTRACT

Objective To determine the protective role of keratinocyte growth factor 2 (KGF-2) on dextran sodium sulfate (DSS)-induced murine colitis and investigate the mechanism of its effect on intestinal mucosal barrier.Methods A total of 36 male C57BL/c mice were divided into 4 groupsnormal control group,DSS model group,model + KGF-2 (5 mg/kg) group and model + KGF-2 (10 mg/kg)group.Groups except the control were added 3.5 ％ DSS in drinking water.Disease activity index (DAD,weight change,colon length loss and histological score were detected to evaluate the protective effect of KGF-2 on colitis.Serum fluorescein isothiocyanate-dextran (FITC-D) permeability were assayed by multiscan spectrum.In order to explore the protective role of KGF-2 on murine intestinal mucosal barrier,ZO-1 and occludin protein concentration were detected by immunohistochemical staining and Western blot.Meanwhile,cytokines including TNF-α,IL-6,IL-10,TGF-1β,IFN-γ and IL-1β in colonictissue were detected by ELISA.Results Compared with DSS-induced colitis model group,10 mg/kg KGF-2 significantly reduced DAI (P =0.021 1),weight loss (P =0.017 6),colon length loss (4.956 ±0.2583 vs.6.289±0.215 7,P =0.001 1),histologicalscore (12.17±1.222 vs.7.000±0.6325,P =0.001 1),and FITC-D permeability (168.5 ± 27.01 vs.14.62 ± 1.812,P =0.004 7) and reversed the downregulation of tight junction (TJ) proteins (ZO-10.158 6 ± 0.010 51 vs.0.387 9 ± 0.028 64,P＜0.000 1;occluding0.300 5 ± 0.026 56 vs.0.445 0 ± 0.056 62,P =0.043 4).Significant decrease of TNF-α (68.93 ± 3.379 vs.40.41 ± 1.576,P＜0.000 1) and increase of IL-6 (3 755 ± 309.8 vs.5 640 ± 418.0,P =0.004 7) and IL-10 (304.0 ± 21.47 vs.521.2 ± 49.40,P =0.002 4) levels were noted in the 10 mg/kg KGF-2 treated mice.The effect of the KGF-2 was dose-dependent.Conclusions KGF-2 could ameliorate DSS-induced colitis and it may be associated with the decrease of the damage of mucosal barrier structure and funcntion by preventing ZO-1 and occludin from downregulating.The protective effect of KGF-2 on intestinal barrier function may also be exerted by inhibition of TNF-α and stimulation of IL-6 and IL-10 secretion.