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   » » Wiki: Macrophage Colony-stimulating Factor
Tag Wiki 'Macrophage Colony-stimulating Factor'.
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The colony stimulating factor 1 ( CSF1), also known as macrophage colony-stimulating factor ( M-CSF), is a secreted which causes hematopoietic stem cells to differentiate into 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 described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the .


Structure
M-CSF is a , 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.

Four transcript variants encoding three different isoforms (a proteoglycan, glycoprotein and cell surface protein) have been found for this gene.


Function
M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the proliferation, differentiation, and survival of , , and bone marrow progenitor cells. M-CSF affects macrophages and monocytes in several ways, including stimulating increased phagocytic and chemotactic activity, and increased tumour cell cytotoxicity. 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.

M-CSF released by (as a result of stimulation by parathyroid hormone) exerts effects on . M-CSF binds to receptors on inducing differentiation, and ultimately leading to increased plasma levels—through the (breakdown) of bone. Additionally, high levels of CSF-1 expression are observed in the endometrial epithelium of the pregnant uterus as well as high levels of its receptor CSF1R in the placental . 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 receptor CSF1R are implicated in the mammary gland during normal development and growth.


Clinical significance
Locally produced M-CSF in the vessel wall contributes to the development and progression of .

M-CSF has been described to play a role in renal pathology including acute kidney injury and chronic . The chronic activation of monocytes can lead to multiple metabolic, hematologic and immunologic abnormalities in patients with chronic kidney failure. In the context of acute kidney injury, M-CSF has been implicated in promoting repair following injury, but also been described in an opposing role, driving proliferation of a pro-inflammatory macrophage phenotype.


As a drug target
PD-0360324 and MCS110 are CSF1 inhibitors in clinical trials for some cancers. Interest Builds in CSF1R for Targeting Tumor Microenvironment See also CSF1R inhibitors.


Interactions
Macrophage colony-stimulating factor has been shown to interact with PIK3R2.


Further reading

External links
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