Significance Of TGFβ Receptors Expressing In Oxazolone Colitis Model In Mice

ObjectivesTo observe the expression of TGFpR Ⅰ , TGFβR Ⅱ and Smad7 in oxazolone induced colitis of mice and find out the mechanism of the abnormality of signal transmission on pathogenesis of colitis. MethodsInduction of colitis :BALB/c mice were presensitized by skin painting with 0.2ml 3% oxazolone in 100% ethanol on day 0 and 1 followed by intrarectal administration of 0.15ml 1% oxazolone in 50% ethanol on day 7.The mice were sacrificed after 3 days.Colitis was evaluated by macroscopic and microscopic score;the expressing and quantity of TGFβR Ⅰ , TGFβR Ⅱ and Smad7 were examined and assayed by immunohistochemical(IHC) and Western blot(WB) respectively.All the results were compared with the controls. Results1 .Experimental group observation:24h after being clystered with oxazolone,the mice presented eating and moving less,loose stool,hematochezia or OB(+),weight loss 4.5% in average,48h and 72h after clysis,the symptoms above aggravated with weight lost 8.3% and 10.3% inaverage respectively.2.The macroscopic and microscopic score in control and experimental group were 0.17±0.41 ^ 2.67±1.03 and 2.33±0.52> 8.17±0.75 respectively.The results showed distinct differences between two groups (both P<0.001),so a chronic colitis model induced by oxazolone was established.3.1mmunohistochemical observation: In normal intestine,TGFPR I ^ TGFpR II ^ Smad7 mainly co-localized on the upper part of the villus,especially luminal surface of the epithelium. In contrast, in experimental intestine these factors not only co-localized throughout the villus including fundus of crypts ,but also showed distinct immunoreactivity in mononuclear cells of the lamina propria and submucosa.So TGF0 may involve in epithelial cell rehabilitation and intestine immune regulation.4.Western blot: the amounts of TGFPR I -. TGFpR II > Smad7 expression in control and experimental group were 3.40±l^ 21.71±6^ 8.95±2.12 and 6.4ftfc2.^ 4.40±3.34, 17.92±6.80 respectively, the ratio of TGFpR I III was 0.16±0.01 and 2.14± 1.61.There was no difference of TGFpR I between two groups(P=0.055>0.05), but significant difference of TGFpRII, Smad7 ? TGFpR I /IIbetween two groups(P<0.01 > P<0.05> PO.01 respectively).So there is TGFP signal abnormality in oxazolone colitis. ConclusionsIncreased TGFpR I / II ratio depresses receptors reacting to TGFP;decreased TGFpR II results in the ineffective activation of TGFpR I ; increased Smad7 can suppress intracellular signal transmission.So we conclude there is abnormality of TGFp signal transmission in Oxazolone induced colitis.Because its pathologic and immunologic characteristicsresemble human UC, we suspect the similar changes in human UC.But theresearch of the abnormality in TGFP signal transmission system need to becontinued.