The international journal "Nature Communications" is sponsored by the Institute of Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Professor White of Baylor University of Medical Sciences, Hui Lijian, researcher at the Institute of Biochemistry, Fang Jing, a researcher at the Shanghai Institute of Biological Sciences, and researchers from the Institute of Nutrition Published online publications of Zhou Bin’s research group Yu Ying and Duan Shengzhong’s latest book: Using Apln-CreER for Genetic Targeting of Germination Angiogenesis. In this study, Apln-CreER transgenic mice were used to successfully track tissue damage, repair, and angiogenesis during tumor growth, and the tool was used to signal angiogenesis and VEGF-VEGFR2 in mice and it blocked This approach has been achieved and a specific inhibitory effect on tumor growth has been achieved.
Blood vessels transport oxygen and nutrients to organs and tissues throughout the body. They are beneficial to tissue growth and regeneration, wound healing, tissue repair and fetal growth, but at the same time they are mediators of inflammation, tumor cell invasion and metastasis. Through the proliferation and migration of vascular endothelial cells based on existing capillaries or venules, the process of sprouting from existing blood vessels to form new capillaries is called angiogenesis. Angiogenesis is an important process of development and growth. The formation of an orderly vascular network is regulated by factors that promote and inhibit angiogenesis. If the balance between the two is lost, illness may occur. In cancer, diabetic eye disease and rheumatoid arthritis, excessive angiogenesis promotes the growth of diseased tissues. In contrast, coronary heart disease, insufficient angiogenesis in stroke and delayed wound healing can lead to poor blood circulation and tissue necrosis. Therefore, angiogenesis is also a target for the treatment of tumors, blindness, coronary heart disease and other diseases. The research and follow-up of angiogenesis markers provide new treatment methods for tumors and angiogenesis-related diseases. Appellin (Apln) is one of the endogenous ligands of the G protein coupled receptor aprin receptor (APJ), and an endogenous peptide with multiple physiological functions. It is involved in regulating cardiovascular function and cardiomyocyte differentiation. And development of the heart. The expression of Apln and APJ is regulated by the HIF family of hypoxia-inducible factors. These factors are highly expressed in developing blood vessels or new blood vessels, but low in steady-state blood vessels. Apln-APJ can also increase blood vessel inner diameter and endothelial cell barrier to promote blood vessel maturation. In addition, Apln-APJ is highly expressed in endothelial cells of various tumors, and by comparing the expression profiles of endothelial cells of tumors and normal tissues, it is considered that it is a gene specifically expressed in tumor endothelial cells.
Liu Qiaozhen, a doctoral student in the
research team, used mouse models of myocardial infarction, hind limb ischemia, subcutaneous tumors and spontaneous tumors to repair the damage during tumor growth and angiogenesis. We studied the marking function of CreER. The results show that Aprn-CreER can effectively mark the angiogenesis of hind limbs after myocardial infarction and ischemic injury, and track tumor angiogenesis. Further studies have shown that Apln is specifically expressed in cells above tumor angiogenesis, which is close to the most hypoxic position of the tumor. This is consistent with the conclusion that Apln is regulated by hypoxia inducers in previous studies. In addition, in this study, Apln-CreER tool mice were used to specifically eliminate angiogenic endothelial cells and block the VEGF-VEGFR2 signaling pathway, thereby achieving an inhibitory effect on tumor growth. This study shows that Apln can effectively track angiogenesis and genetically manipulate the gene expression of angiogenesis, providing a new tool for basic research on tumor anti-angiogenesis.