IGF-I increases IGFBP-5 and collagen alpha(1)(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells
文献类型：期刊论文
| 作者 | Xin, XP; Hou, YT; Li, LN; Schmiedlin-Ren, P; Christmas, GM; Cheng, HL; Bitar, KN; Zimmermann, EM |
| 刊名 | AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
 |
| 出版日期 | 2004-05-01 |
| 卷号 | 286期号:5页码:G777-G783 |
| 关键词 | insulin-like growth factor I signal transduction Crohn's disease inflammatory bowel disease |
| ISSN号 | 0193-1857 |
| DOI | 10.1152/ajpgi.00293.2003 |
| 文献子类 | Article |
| 英文摘要 | IGF-I is a potent fibrogenic growth factor that stimulates proliferation of intestinal smooth muscle cells and increases synthesis of collagen and IGF-I-binding proteins by the cells. These processes contribute to intestinal fibrosis that develops in patients with Crohn's disease and in Lewis-strain rats with experimental Crohn's disease. The aim of this study was to determine which early docking proteins are associated with IGF-I receptor signal transduction and which transduction pathway is involved in IGF-I-mediated gene regulation in intestinal smooth muscle cells. Primary cultures of smooth muscle cells isolated from the muscularis externa of the distal colon of Lewis rats were treated with IGF-I ( 100 ng/ml). Immunoprecipitation studies demonstrated that IGF-I stimulation resulted in tyrosine phosphorylation of IRS-1, IRS-2, and Shc. Coimmunoprecipitation demonstrated a close association between the IGF-I receptor and these three early docking proteins. Concurrent treatment with the MAPK inhibitor PD98059 ( 10 muM) resulted in an inhibition of the IGF-I-mediated increase in IGFBP-5 and collagen alpha(1)(I) mRNAs, while concurrent treatment with the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin (100 nM) had no effect. In additional experiments, cells were transiently transfected with adenoviral vectors dominantly expressing inactive mutant Akt or constitutively expressing wild-type Akt. In both cases, the IGF-I-mediated increase in collagen I protein did not differ from that observed in control cultures that had been transfected with an adenoviral vector carrying the LacZ reporter gene. These results suggest that the MAPK pathway is key to IGF-I-mediated gene regulation in intestinal smooth muscle cells, whereas data do not suggest a role for the Akt-dependent pathway in our system. |
| WOS关键词 | GROWTH-FACTOR-I ; FACTOR BINDING PROTEIN-5 ; CROHNS-DISEASE ; EXPERIMENTAL COLITIS ; PLASMA-MEMBRANE ; GENE-EXPRESSION ; KINASE B/AKT ; ACTIVATION ; ENTEROCOLITIS ; TARGET |
| 资助项目 | NIDDK NIH HHS[R01 DK-56750] ; NIDDK NIH HHS[5-P30-DK-34933] |
| WOS研究方向 | Gastroenterology & Hepatology ; Physiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000220693200012 |
| 出版者 | AMER PHYSIOLOGICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274081]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zimmermann, EM |
| 作者单位 | 1.Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA 2.Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA 3.Univ Michigan, Sch Med, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA 4.Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI 48109 USA 5.Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xin, XP,Hou, YT,Li, LN,et al. IGF-I increases IGFBP-5 and collagen alpha(1)(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells[J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,2004,286(5):G777-G783. |
| APA | Xin, XP.,Hou, YT.,Li, LN.,Schmiedlin-Ren, P.,Christmas, GM.,...&Zimmermann, EM.(2004).IGF-I increases IGFBP-5 and collagen alpha(1)(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells.AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,286(5),G777-G783. |
| MLA | Xin, XP,et al."IGF-I increases IGFBP-5 and collagen alpha(1)(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells".AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY 286.5(2004):G777-G783. |
入库方式： OAI收割
来源：上海药物研究所
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