Expression of MMP-2, MMP-7, MMP-9, and TIMP-1 by Inflamed Mucosa in the Initial Diagnosis of Ulcerative Colitis as a Response Marker for Conventional Medical Treatment

Abstract

<b><i>Introduction:</i></b> Experimental and clinical data involve matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of inflammatory bowel diseases. However, the impact of MMPs/TIMPs expression by inflamed mucosa on medical response therapy has scarcely been investigated. <b><i>Methods:</i></b> The expression of MMP-2, MMP-7, MMP-9, and TIMP-1 was determined by immunohistochemical analysis in inflamed mucosa samples at diagnosis in 82 patients with ulcerative colitis (UC; 22 never-treated with corticosteroids, 28 nonresponders, and 32 responders to corticosteroid therapy) and 15 patients with acute diverticulitis (AD). The global expression (score value) of each factor was analyzed by computer-generated image analysis. <b><i>Results:</i></b> UC samples showed higher MMP-2 and MMP-9 expression but lower TIMP-1 expression than the AD samples (<i>p</i> &#x3c; 0.0001, for all). High MMP-9 and TIMP-1 scores were significantly associated with no need for corticosteroid treatment (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.017, respectively); whereas higher score in the MMP-7 expression was significantly associated with nonresponse to corticosteroid therapy (<i>p</i> = 0.037). In addition, in this latter UC subgroup, MMP-7 correlated positively with the younger age of the patients and with the extension of the disease (<i>p</i> = 0.030 and <i>p</i> = 0.010, respectively). <b><i>Conclusion:</i></b> Our results suggest the relevance of MMPs and TIMPs for predicting treatment response to both 5-aminosalicylates and corticosteroids in UC.