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The secret to maintaining hematopoietic stem cells: How does angiopoietin-1 affect cell survival in the bone marrow?
Recent studies have shown that the angiogenic factor angiopoietin-1 plays a key role in maintaining the survival and stability of hematopoietic stem cells (HSCs). These findings will undoubtedly provide new perspectives for our understanding of the survival mechanisms of cells in the bone marrow and may have important clinical significance for the treatment of blood diseases.
Angiopoietin is a key factor in the angiogenesis process, which helps the maturation and stability of new blood vessels.
The angiopoietin family consists of four known members: ANGPT1, ANGPT2, ANGPTL3, and ANGPT4. Among them, angiopoietin-1 is essential for the maturation and stability of blood vessels, while angiopoietin-2 may cause cell apoptosis, thereby destroying vascularization. However, when angiopoietin-2 works together with vascular endothelial growth factor (VEGF), it can promote the formation of new blood vessels.
Structurally, angiopoietins are characterized by an N-terminal superaggregation region, a central helical region, a linker region, and a C-terminal fibrin-related region, which together are responsible for the binding between their ligands and receptors. Both angiopoietin-1 and angiopoietin-2 can form dimers, trimers and tetramers, among which only structures above tetramer can activate tyrosine kinase receptors.
The signaling of these receptors primarily affects the growth and function of vascular endothelial cells. Tie-2 receptor is the main receptor of angiopoietin-1. Its activation can promote the interaction and stabilization of HSC with the extracellular matrix and further support the dormant state of HSC, which is the key to maintaining its long-term regenerative capacity.
Tie-2/Ang-1 signaling is essential for the long-term maintenance of HSCs and their survival in the bone marrow.
Specifically, activation of the Tie-2 receptor promotes the adhesion and migration of HSCs, ensuring their proliferation and survival in the bone marrow. Regulation of this signaling pathway also helps HSCs resist various cellular stresses, such as hypoxia or inflammation, protecting them from damage. This phenomenon is evident in endothelial cells and specific macrophages in the bone marrow.
In addition, angiopoietin-1 has good physiological properties because it is produced in vascular supporting cells, and it is also considered a potential target for the treatment of blood diseases. Regarding blocked angiogenesis, researchers have demonstrated that angiopoietin-2 can also act as a regulator of signal transduction, negatively affecting vascular stability.
In the absence of VEGF, expression of angiopoietin-2 may lead to endothelial cell death and vascular regression.
In cancer, the expression of angiopoietin-2 is closely related to the progression of tumors. Studies have shown that the level of angiopoietin-2 is positively correlated with the clinical characteristics of various tumors. Therefore, controlling the expression of angiopoietin-2 may provide new ideas for cancer treatment. Various clinical trials are also exploring the use of drugs that block angiopoietin-2 to reduce tumor angiogenesis and thereby prevent tumor growth and spread.
Finally, the study of the function of angiopoietin and its role in the survival of hematopoietic stem cells not only enriches our understanding of biology, but also provides a valuable scientific basis for future clinical applications and the development of therapeutic strategies. In this context, we can't help but wonder how to effectively use these mechanisms in clinical practice to improve patient prognosis?
