NOVEL HEPARIN-BINDING GROWTH FACTOR IN UTERINE FLUID

子宫液中新型肝素结合生长因子

• 批准号: 2403303
• 负责人: DAVID R BRIGSTOCK
• 金额: $ 9.95万
• 依托单位: CHILDREN'S HOSPITAL (COLUMBUS)
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2403303
• 关键词: 3T3 cells; affinity chromatography; binding proteins; cell membrane; complementary DNA; embryo /fetus; endometrium; enzyme linked immunosorbent assay; extracellular matrix; fibroblast growth factor; genetic mapping; growth factor receptors; heparin; intermolecular interaction; laboratory rabbit; protein purification; protein sequence; protein structure function; receptor binding; secretion; swine; synthetic peptide; uterus; western blottings

The broad, long-term objectives of this work are to elucidate the nature and function of uterine secretory growth factors that regulate the growth of the extra-embryonic membranes of the blastocyst and/or proliferation of endometrial epithelium or stroma. This proposal focusses on the characterization of a novel growth factor in pig uterine luminal flushing that is elevated in early pregnancy. This factor, a cationic, 10,000-Mr, heat-labile, acid-labile mitogen for fibroblasts, smooth muscle and endometrial cells, has been termed "heparin-binding growth factors. The specific aims of this project are 1) TO isolate and molecularly characterize HBGF-0.8; 2) To analyze the nature and functional significance of heparin-HBGF-0.8 interactions; 3) To quantify HBGF-0.8 in uterine fluids; and 4) To study HBGF-0.8 receptor localization and function in the uterine tract. The health relatedness of this project is that HBGF-0.8 may (i) promote blastocyst development and reduce the incidence of embryonic mortality in utero or after in vitro fertilization and (ii) stimulate cyclic endometrial remodelling or contribute to the onset and progression of uterine tract cancers. The research design and methods are to purify HBGF-0.8 to homogeneity using preparative column chromatography (e.g. cation exchange, heparin-affinity, reverse-phase) and to determine this amino acid sequence directly or indirectly by cloning and sequencing its cDNA. Purified HBGF-0.8 will be labelled with I to study (i) its binding to heparin-like molecules in extracellular matrix and cell surfaces (ii) the nature of its specific high affinity receptors and (iii) the presence of functional HBGF-0.8 receptors on freshly isolated or cultured endometrial or trophoderm cells. The effect of heparin on mediating HBGF-0.8 will be mapped by determining which synthetic HBGF-0.8 peptides bind to heparin and modulate binding of HBGF- 0.8 to heparin. Rabbits will be immunized with synthetic peptides that are conjugated to a promiscuous tetanus toxoid T-cell epitope. Specific anti-HBGF-0.8 antibodies will be selected by ELISA. Antisera will be used to screen recombinant gammagt11 for HBGF-0.8, to immunolocalize HBGF-0.8 in uterine sections, to quantify HBGF-0.8 competitive ELISA in uterine flushing from estrous, pregnant, or steroid-treated pigs, and for detecting HBGF-0.8 on Western blots.

这项工作的广泛、长期目标是阐明其性质

项目成果

Localization of connective tissue growth factor during the period of embryo implantation in the mouse.

• DOI: 10.1095/biolreprod59.5.1207
• 发表时间: 1998-11
• 期刊: Biology of reproduction
• 影响因子: 3.6
• 作者: G. A. Surveyor;Amy K. Wilson;D. Brigstock

Localization of connective tissue growth factor in human uterine tissues.

结缔组织生长因子在人体子宫组织中的定位。

• DOI: 10.1093/molehr/6.12.1093
• 发表时间: 2000
• 期刊: Molecular human reproduction
• 影响因子: 4
• 作者: Uzumcu,M;Homsi,MF;Ball,DK;Coskun,S;Jaroudi,K;Hollanders,JM;Brigstock,DR
• 通讯作者: Brigstock,DR

The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family.

• DOI: 10.1210/edrv.20.2.0360
• 发表时间: 1999-04
• 期刊: Endocrine reviews
• 影响因子: 20.3
• 作者: D. Brigstock

Characterization of the gene encoding murine heparin-binding epidermal growth factor-like growth factor.

编码鼠肝素结合表皮生长因子样生长因子的基因的表征。

• DOI: 10.1016/0378-1119(95)00861-6
• 发表时间: 1996
• 期刊: Gene
• 影响因子: 3.5
• 作者: Harding,PA;Brigstock,DR;Shen,L;Crissman-Combs,MA;Besner,GE
• 通讯作者: Besner,GE

Induction of anchorage independent growth by heparin-binding EGF-like growth factor (HB-EGF).

通过肝素结合 EGF 样生长因子 (HB-EGF) 诱导贴壁独立生长。

• DOI: 10.3109/08977199909001062
• 发表时间: 1999
• 期刊: Growth factors (Chur, Switzerland)
• 作者: Harding,PA;Davis-Fleischer,KM;Crissman-Combs,MA;Miller,MT;Brigstock,DR;Besner,GE
• 通讯作者: Besner,GE