| 1 | CTGF, intestinal stellate cells and carcinoid fi brogenesis显示文摘AIM: To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGFβ1 and CTGF, in the mediation of fi brosis via activation of an 'intestinal' stellate cell. METHODS: GI carcinoid tumors were collected for Q RT-PCR analysis of CTGF and TGFβ1. Markers of stellate cell desmoplasia were identified in peritoneal fibrosis by immunohistochemistry and stellate cells cultured from fresh resected fibrotic tissue. CTGF and TGFβ1 were evaluated using quantitative tissue array profi ling (AQUA analysis) in a GI carcinoid tissue microarray (TMA) with immunostaining and correlated with clinical and histologically documented fi brosis. Serum CTGF was analyzed using a sandwich ELISA assay. RESULTS: Message levels of both CTGF and TGFβ1 in SI carcinoid tumors were signifi cantly increased (> 2-fold, P < 0.05) versus normal mucosa and gastric (non-f ibrotic) carcinoids. Activated stellate cells and markers of stellate cell-mediated fi brosis (vimentin, desmin) were identifi ed in histological fibrosis. An intestinal stellate cell was immunocytochemically and biochemically characterized and its TGFβ1 (10-7M) initiated CTGF transcription response (> 3-fold, P < 0.05) demonstrated. In SI carcinoid tumor patients with documented fi brosis, TMA analysis demonstrated higher CTGF immunostaining (AQUA Score: 92 ± 8; P <0.05), as well as elevated TGFβ1 (90.6 ± 4.4, P < 0.05). Plasma CTGF (normal 12.5 ± 2.6 ng/mL) was increased in SI carcinoid tumor patients (31 ± 10 ng/mL, P < 0.05) compared to non-fi brotic GI carcinoids (< 15 ng/mL).CONCLUSION: SI carcinoid tumor fibrosis is a CTGF/ TGFβ1-mediated stellate cell-driven fibrotic response. The delineation of the biology of fibrosis will facilitate diagnosis and enable development of agents to obviate its local and systemic complications. | M Kidd IM Modlin MD Shapiro RL Camp SM Mane W Usinger JR Murren | 2007 | World Journal of Gastroenterology2007，13，39： | 5 |
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