Hormi K, Cadiot G, Kermorgant S, Dessirier V, Le Romancer M, Lewin M J, Mignon M, Lehy T
Department of Gastroenterology, Hôpital Bichat, Paris, France.
Growth Factors. 2000;18(2):79-91. doi: 10.3109/08977190009003235.
Transforming growth factor-alpha (TGF-alpha) is overexpressed in colonic carcinomas and promotes mucosal wound healing. It may be implicated in chronic inflammatory bowel disease (IBD). We analyzed the expression of TGF-alpha and its receptor, epidermal growth factor receptor (EGF-r), in the colonic mucosa of patients with Crohn's disease (CD) or ulcerative colitis (UC), in active or inactive stages, as compared with controls. Proteins and mRNA were detected in biopsies from the right and left colon and in surgical colonic specimens. Immunoblot analysis revealed TGF-alpha protein as a 29 kDa band. This band was normally expressed in uninvolved colonic mucosa of patients with CD or UC whether in active or inactive stages, but decreased or absent in involved mucosa of active IBD, even when TGF-alpha mRNA and EGF-r protein were detected. In the unaffected mucosa of CD, the intensity of TGF-alpha immunoreactivity was similar to that of controls in the right colon but stronger (P = 0.05) in the left colon. There was no TGF-alpha overexpression in dysplastic regions. In conclusion, in active IBD disease, the decreased TGF-alpha protein amount seems not only related to epithelial cell loss but reflects a down-regulation at least at the protein level. We speculate that TGF-alpha does not play a role within the active stage but may be implicated later in the repair process.
转化生长因子-α(TGF-α)在结肠癌中过度表达,并促进黏膜伤口愈合。它可能与慢性炎症性肠病(IBD)有关。我们分析了克罗恩病(CD)或溃疡性结肠炎(UC)患者处于活动期或非活动期时结肠黏膜中TGF-α及其受体表皮生长因子受体(EGF-r)的表达,并与对照组进行比较。在左右结肠活检组织及手术切除的结肠标本中检测蛋白质和mRNA。免疫印迹分析显示TGF-α蛋白为一条29 kDa的条带。这条带在CD或UC患者未受累的结肠黏膜中正常表达,无论处于活动期还是非活动期,但在活动期IBD的受累黏膜中减少或缺失,即使检测到TGF-α mRNA和EGF-r蛋白时也是如此。在CD未受影响的黏膜中,TGF-α免疫反应强度在右结肠与对照组相似,但在左结肠更强(P = 0.05)。发育异常区域未出现TGF-α过度表达。总之,在活动期IBD中,TGF-α蛋白量的减少似乎不仅与上皮细胞丢失有关,至少在蛋白质水平上反映了一种下调。我们推测TGF-α在活动期不起作用,但可能在后期修复过程中发挥作用。