Stromal cell-derived factor 1
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 10: 44.37 – 44.39 Mb | Chr 6: 117.15 – 117.16 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
The stromal cell-derived factor 1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a
Structure
Gene
The CXCL12 gene resides on chromosome 10 at the band 10q11.21 and contains 4
Protein
This protein belongs to the
Function
CXCL12 is expressed in many tissues in mice including
In adulthood, CXCL12 plays an important role in angiogenesis by recruiting endothelial progenitor cells (EPCs) from the bone marrow through a CXCR4 dependent mechanism.[21]
CXCR4, previously called LESTR or fusin, is the receptor for CXCL12.[16] This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently, it was suggested that CXCL12 may also bind the CXCR7 receptor (now called ACKR3).[22][23][24] By blocking CXCR4, a major coreceptor for HIV-1 entry, CXCL12 acts as an endogenous inhibitor of CXCR4-tropic HIV-1 strains.[25]
CNS
During embryonic development, CXCL12 plays a role in cerebellar formation through the migration of neurons.[26] Within the CNS, CXCL12 contributes to cell proliferation, neurogenesis (nervous tissue development and growth), as well as neuroinflammation. Neural progenitor cells (NPCs) are stem cells that differentiate into glial and neuronal cells. CXCL12 promotes their migration to lesion sites within the brain, specifically over extensive ranges. Once at the site of damage, NPCs may begin stem cell based tissue repair to the lesion.[27] The CXCL12/CXCR4 axis provides guidance cues for axons and neurites hence promoting neurite outgrowth (neurons forming projections) and neurogenesis.[28] Like other chemokines, CXCL12 is involved with cell migration that contributes to inflammation. In regards to the CNS, CXCL12 plays a role in neuroinflammation by attracting leukocytes across the blood brain barrier.[27] however, excessive production and accumulation of CXCL12 can become toxic and the inflammation produced may result in serious consequences.[29]
Clinical significance
In humans, CXCL12 has been implicated in a wide variety of biomedical conditions involving several organ systems.[30] Furthermore, CXCL12 signaling in conjunction with CXCR7 signaling has been implicated in the progression of pancreatic cancer.[7] In the urinary tract system, methylation of the CXCL12 promoter and expression of PD-L1 may be powerful prognostic biomarkers for biochemical recurrence in prostate carcinoma patients after radical prostatectomy, and further studies are ongoing to confirm if CXCL12 methylation may aid in active surveillance strategies.[31] In the field of oncology, melanoma associated fibroblasts are stimulated by stimulation of the A2B adenosine receptor followed by stimulation of fibroblast growth factor and increased expression of CXCL12.[8]
Clinical marker
A multi-locus genetic risk score study based on a combination of 27 loci, including the CXCL12 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[9]
Multiple Sclerosis
A neurological condition that results from a faulty interaction between the immune and nervous systems in multiple sclerosis. MS is characterized by demyelination of nerves due to the body's immune system attacking the CNS. Elevated levels of CXCL12 are observed in the cerebral spinal fluid of patients with MS. CXCL12 crosses the blood–brain barrier and causes neuroinflammation that contributes to axonal damage and therefore the progression of multiple sclerosis.[32][unreliable medical source]
Alzheimer's disease
Though CXCL12 may be detrimental for those with MS, recent research is suggesting that this chemokine may be beneficial in decreasing the progression of patients with Alzheimer's. Alzheimer's is another neurological condition and the most common form of dementia where cognition significantly declines. One main characteristic of Alzheimer's is the accumulation of a brain plaque known as beta-amyloid. There are neuroprotective aspects of CXCL12 in mice with these plaques/Alzheimer's. PAK is a protein associated with maintaining dendritic spines, which are essential at synapses in receiving information from axons. Mislocalization of PAK occurs in patients with Alzheimer's, however pretreatment of neurons in mice with CXCL12 showed a suppression of that mislocalization.[33][unreliable medical source] Additionally, this pretreatment with CXCL decreased the prevalence of apoptosis and oxidative damage normally caused by the presence of the beta-amyloid plaque.[33]
As a drug target
Chemokines and chemokine receptors, of which CXCR stands out, regulate multiple processes such as morphogenesis, angiogenesis, and immune responses and are considered potential targets for drug development. It is indicated by clinical samples that a high expression level of CXCR4 in
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000107562 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000061353 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)".
- ^ "BioGPS - your Gene Portal System". biogps.org. Retrieved 11 October 2016.
- ^ PMID 27542220.
- ^ PMID 27590504.
- ^ PMID 25748612.
- ^ "CXCL12 gene information - The Human Protein Atlas". www.proteinatlas.org. Retrieved 20 March 2024.
- ^ a b "CXCL12 - Stromal cell-derived factor 1 precursor - Homo sapiens (Human) - CXCL12 gene & protein". UniProt.
- PMID 14525775.
- PMID 9384579.
- PMID 11953881.
- PMID 35909816.
- ^ PMID 9064327.
- PMID 12684531.
- S2CID 24354002.
- PMID 9689100.
- PMID 24395111.
- S2CID 13616442.
- PMID 16107333.
- PMID 16940167.
- PMID 21300915.
- S2CID 4233446.
- S2CID 29689159.
- ^ PMID 22784557.
- PMID 24639628.
- PMID 24639628.
- PMID 27363619.
- PMID 27462860.
- PMID 16280350.
- ^ PMID 21704645.
- PMID 32104240.
- S2CID 3493909.
- ^ De Clercq E. (2019) Mozobil(R) (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration. Antivir Chem Chemother 27:1.
Further reading
- Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ (August 2005). "Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis". Stem Cells. 23 (7): 879–94. S2CID 22504846.
- Kryczek I, Wei S, Keller E, Liu R, Zou W (March 2007). "Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis". American Journal of Physiology. Cell Physiology. 292 (3): C987–95. S2CID 7423893.
- Stellos K, Gawaz M (March 2007). "Platelets and stromal cell-derived factor-1 in progenitor cell recruitment". Seminars in Thrombosis and Hemostasis. 33 (2): 159–64. S2CID 260320898.
- Wang J, Liu X, Lu H, Jiang C, Cui X, Yu L, Fu X, Li Q, Wang J (March 2015). "CXCR4(+)CD45(-) BMMNC subpopulation is superior to unfractionated BMMNCs for protection after ischemic stroke in mice". Brain, Behavior, and Immunity. 45: 98–108. PMID 25526817.
- Arya M, Ahmed H, Silhi N, Williamson M, Patel HR (2007). "Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration". Tumour Biology. 28 (3): 123–31. S2CID 44356923.
PDB gallery | |
|---|---|
|
