{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:34:25Z","timestamp":1791012865002,"version":"4.1.0"},"reference-count":46,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background and Aims:<\/jats:title>\n                  <jats:p>In addition to its crucial role in dampening tissue-damaging immune responses in the gut, transforming growth factor \u03b2 (TGF\u03b2) is a potent profibrogenic agent inducing collagen synthesis and regulating the balance between matrix-degrading matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). TGF\u03b2 signalling was investigated by analysis of Smad proteins and MMPs\/TIMPs in the mucosa overlying strictures in patients with Crohn\u2019s disease (CD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>Specimens were collected from macroscopically normal mucosa overlying strictured and non-strictured gut of patients with fibrostenosing CD. Isolated myofibroblasts were cultured with anti-TGF\u03b2 blocking antibody or TGF\u03b21. TGF\u03b2 transcripts were analysed by quantitative reverse transcription-PCR (RT-PCR). Smad proteins and MMPs were determined by immunoblotting. MMP-12 activity was measured by a real-time MMP-12 activity assay. An in vitro wound-healing scratch assay was used to assess myofibroblast migration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>TGF\u03b2 transcripts, phosphorylated Smad2\u2013Smad3 (pSmad2\u20133) and TIMP-1 proteins were higher in mucosa overlying strictures than in mucosa overlying non-strictured areas. In contrast, mucosa overlying strictured gut had lower expression of Smad7, MMP-12 and MMP-3. Myofibroblasts from mucosa overlying strictured gut showed higher TGF\u03b2 transcripts, a greater pSmad2\u20133 response to TGF\u03b2, increased TIMP-1, lower Smad7, increased collagen production and reduced migration ability compared with myofibroblasts from mucosa overlying non-strictured gut. TGF\u03b2 blockade increased myofibroblast MMP-12 production and migration, more obviously in myofibroblasts isolated from mucosa overlying non-strictured compared with strictured gut.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Changes in TGF-\u03b2 signalling and MMP production were identified in the mucosa overlying strictures in CD which may give a window into the process of fibrosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gut.2008.149096","type":"journal-article","created":{"date-parts":[[2009,2,7]],"date-time":"2009-02-07T03:58:49Z","timestamp":1233979129000},"page":"777-789","source":"Crossref","is-referenced-by-count":193,"title":["Transforming growth factor \u03b2 signalling and matrix metalloproteinases in the mucosa overlying Crohn\u2019s disease strictures"],"prefix":"10.1136","volume":"58","author":[{"given":"A","family":"Di 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