The role of integrins on megakaryocyte development and function
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Integrins are cell surface receptors mainly involved with cell-cell adhesion and cell adhesion to extracellular matrix (ECM) proteins. Integrin signaling participates in many cellular pathways and has multiple effects on cell behavior. The role of integrins on megakaryocytes (MKs) has been extensively studied, and integrins have been proven to be vital in regulating MK development and functions. MKs are large platelet-producing cells primarily residing in the bone marrow (BM). The interactions between MK and ECM proteins in the BM via integrins are thought to play an important role in maintaining normal thrombopoiesis, and deregulation of integrin signaling may lead to impaired MK maturation, MK migration, and proplatelet formation. Integrins also take part in the cell-cell adhesion of MK to other cells in the BM, such as osteoblasts and fibroblasts. MK adhesion is proved to stimulate the expansion of fibroblasts and osteoblasts, which may have strong implications for treating bone marrow fibrosis (BMF) and osteoporosis. In this review, we introduce different types of integrins expressed on MK and discuss their roles during MK differentiation and maturation from hematopoietic stem cells (HSCs) as well as their functions during thrombopoiesis. We also focus on surveying the interactions of MK with other BM cells via integrin signaling and examining the functions of MK integrins in regulating BM homeostasis. Finally, we explain diseases caused by defects associated with MK integrins and explore potential therapeutic treatments.