1998 Russell et al in matrix culture without growth factor in human umbilical vein endothelial cells (HUVEC), the addition of recombinant NRG 3 (a ErbB3 ErbB4 ligand) culture 10d, found that NRG 3 (100ng ml) allows the number of HU VEC an increase of 25 times with 10ng ml the effect of vascular endothelial growth factor (VEGF). Applications can significantly inhibit VEGF-stimulated cells increase in the number of anti-VEGF antibody, but not affect NRG 3 due to the number of HUVEC increased, indicating that NRG 3 HUVEC proliferation effect has nothing to do with VEGF. HUVEC, its application of the two-dimensional collagen gel matrix culture by adding 24 ~ 36h after NRG 3 lumen-like structures formed lengthwise in HUVEC, will not affect the anti-VEGF antibody NRG this angiogenic effect. Corneal angiogenesis model in rats applications containing different doses of NRG or VEGF sustained-release tablets implanted eyes of 7d found, 10ngNRG can induce new blood vessel formation, 50ng can significantly promote new blood vessel formation; role of VEGF similar but does not rely on VEGF. Bagheri is found that The HRG stimulate of breast cancer the epithelial cells VEGFmRNA and protein expression, adding HRG1 to 9hVEGFmRNA increased 2-6 times, can stimulate endothelial cells to produce luminal-like structure, the application of anti-HER2 monoclonal antibody or anti-VEGF monoclonal antibodies this effect can be blocked, this angiogenesis is VEGF dependent. Yen also observed in other tumor cells to a similar result.
Neuregulin (Neuregulins, NRGs), a member of the epidermal growth factor (EGF) family, a local role of polypeptide regulatory factors, plays an important role of the nervous system, such as NRGs promote the proliferation of Schwann cells and glial cells, differentiation adhesion, migration, and survival. Known NRGs, NRG1, NRG2, NRG3 and NRG4 four subtypes. The NRG1 Department with a gene encoding a product separation and purification and cloning in different laboratories, it is a different name, such as neu differentiation factor (of neu differentiationfactor NDF), human heregulin (HRG), glial growth factor (GGF) and acetylcholine the re ceptor inducing the activity (ARIA). In addition, three different genes encoding other types of neuregulin, respectively, NRG2, NRG3 and NRG4. Functional receptors for NRGs ErbBs, also known as epidermal growth factor receptor (EGFR), including four subtypes: ErbB1 of EGFR, ErbB2 of HER2 of neu of ErbB3 of HER3 and ErbB4 is HER4. NRGs and ErbBs receptor activation of the ErbB receptor tyrosine kinase induced by a wide range of biological effects, such as cell proliferation, differentiation, migration, adhesion, survival. Recent studies have shown that NRG of ErbB signaling pathway also plays an important role in the development process of the cardiovascular system, and to participate in the pathogenesis of cardiac hypertrophy.