Thecolony stimulating factor 1 (CSF1), also known asmacrophage colony-stimulating factor (M-CSF), is a secretedcytokine which causeshematopoietic stem cells to differentiate intomacrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally describedcolony-stimulating factors. M-CSF binds to thecolony stimulating factor 1 receptor. It may also be involved in development of theplacenta.[5]
M-CSF is acytokine, being a smaller protein involved in cell signaling. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors.[5]
Four transcript variants encoding three different isoforms (a proteoglycan, glycoprotein and cell surface protein)[6] have been found for this gene.[5]
M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the proliferation, differentiation, and survival ofmonocytes,macrophages, and bone marrow progenitor cells.[7] M-CSF affects macrophages and monocytes in several ways, including stimulating increased phagocytic and chemotactic activity, and increased tumour cell cytotoxicity.[8]The role of M-CSF is not only restricted to the monocyte/macrophage cell lineage. By interacting with its membrane receptor (CSF1R or M-CSF-R encoded by the c-fms proto-oncogene), M-CSF also modulates the proliferation of earlier hematopoietic progenitors and influence numerous physiological processes involved in immunology, metabolism, fertility and pregnancy.[9]
M-CSF released byosteoblasts (as a result ofendocrine stimulation byparathyroid hormone) exertsparacrine effects onosteoclasts.[10] M-CSF binds to receptors onosteoclasts inducing differentiation, and ultimately leading to increased plasmacalcium levels—through theresorption (breakdown) of bone[citation needed]. Additionally, high levels of CSF-1 expression are observed in the endometrial epithelium of the pregnant uterus as well as high levels of its receptorCSF1R in the placentaltrophoblast. Studies have shown that activation of trophoblastic CSF1R by local high levels of CSF-1 is essential for normal embryonic implantation and placental development. More recently, it was discovered that CSF-1 and its receptorCSF1R are implicated in the mammary gland during normal development andneoplastic growth.[11]
Locally produced M-CSF in the vessel wall contributes to the development and progression ofatherosclerosis.[12]
M-CSF has been described to play a role in renal pathology including acute kidney injury and chronickidney failure.[13][14] The chronic activation of monocytes can lead to multiple metabolic, hematologic and immunologic abnormalities in patients with chronic kidney failure.[13] In the context of acute kidney injury, M-CSF has been implicated in promoting repair following injury,[15] but also been described in an opposing role, driving proliferation of a pro-inflammatory macrophage phenotype.[16]
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Takahashi M, Hirato T, Takano M, Nishida T, Nagamura K, Kamogashira T, Nakai S, Hirai Y (June 1989). "Amino-terminal region of human macrophage colony-stimulating factor (M-CSF) is sufficient for its in vitro biological activity: molecular cloning and expression of carboxyl-terminal deletion mutants of human M-CSF".Biochemical and Biophysical Research Communications.161 (2):892–901.doi:10.1016/0006-291X(89)92683-1.PMID2660794.
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