“Allograft inflammatory factor 1”的意思、由来-开放百科全书

The AIF1 gene is located within a segment of the major histocompatibility complex class III region. It has been shown that this gene is highly expressed in testis, spleen, and brain but weakly expressed in lung, and kidney. Among brain cells, the Iba1 gene is strongly and specifically expressed in microglia. Circulating macrophages also express Iba1.

Function

AIF1 is a protein that exists in the cytoplasm, and it is highly evolutionarily conserved. It is also possibly identical to three other proteins, Iba-2, MRF-1 (microglia response factor) and daintain. However complete functional profiles of all three proteins and how they overlap is unknown.^[3] IBA1 is a 17-kDa EF hand protein that is specifically expressed in macrophages / microglia and is upregulated during the activation of these cells. Iba1 expression is up-regulated in microglia following nerve injury,^[4] central nervous system ischemia, and several other brain diseases.

AIF1 was originally discovered in atherosclerotic lesions in a rat model of chronic allograft cardiac rejection. It was found to be upregulated in macrophages and neutrophils in response to the cytokine IFN-γ.^[5] AIF1 expression has been seen to increase in vascular tissue in response to arterial injury, specifically it is found in activated vascular smooth muscle cells in response to IFN-γ, IL-1β, and T-cell conditioned media.^[6] In vascular smooth muscle cells, activation is responsible for arterial thickening in allografts through over proliferation. AIF1 has been found to enhance growth and promote proliferation in vascular smooth muscle cells through deregulation of the cell cycle. It does this by shortening the cell cycle and altering the expression of cyclins.^[7] Though histologically different, AIF1 has also been shown to promote the proliferation and activation of endothelial cells (EC). EC activation, leads to proliferation and migration of cells, which is involved in multiple normal vascular processes, such as atherosclerosis, angiogenesis, and wound healing. It is currently theorized that AIF1 works to control endothelial cell proliferation and migration through action in signal transduction pathways.^[8] It has features of a cytoplasmic signaling protein, including several domains that allow for binding to multiprotein complexes, called PDZ domains.^[9] In endothelial cells, AIF1 has been specifically shown to regulate vasculogenesis, including the formation of aortic sprouting and tube-like formations. AIF1 been shown to interact with kinase p44/42 and PAK1, two previously known signal transduction molecules, in regulating these processes. AIF1 also shows distinct differences in the pathways by which it regulates endothelial cells, macrophages, and vascular smooth muscle cells.^[8]

Clinical significance

Allograft Inflammatory Factor 1 is found in activated macrophages. Activated macrophages are found in tissues with inflammation. AIF1 levels in healthy humans have been found to positively correlate with metabolic indicators, such as body mass index, triglycerides, and fasting plasma glucose levels. The excess of adipose tissue found in obese patients is found to cause chronic inflammation with an increase in the number of activated macrophages. Subsequently, AIF1 may be an accurate indicator of macrophage activation in the body.^[10] There is also evidence that AIF1 could be a marker for diabetic nephropathy when detected in serum.^[11] Since diabetic nephropathy is a consequence of long-term type 1 and type 2 diabetes, this consistent with evidence that AIF1 may be associated with other aspects of diabetes. It is found in activated macrophages in the pancreatic islets, and has been shown to decrease insulin secretion, while simultaneously impairing glucose elimination.^[12]

References

1. ^{{cite journal | author = Autieri MV | title = cDNA cloning of human allograft inflammatory factor-1: tissue distribution, cytokine induction, and mRNA expression in injured rat carotid arteries | journal = Biochem Biophys Res Commun | volume = 228 | issue = 1 | pages = 29–37 |date=Dec 1996 | pmid = 8912632 | pmc = | doi = 10.1006/bbrc.1996.1612 }}
2. ^{{cite web | title = Entrez Gene: AIF1 allograft inflammatory factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=199| accessdate = }}
3. ^{{cite journal | vauthors = Deininger MH, Meyermann R, Schluesener HJ | title = The allograft inflammatory factor-1 family of proteins | journal = FEBS Lett. | volume = 514 | issue = 2–3 | pages = 115–21 |date=March 2002 | pmid = 11943136 | doi = 10.1016/S0014-5793(02)02430-4 }}
4. ^{{cite journal | vauthors = Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S | title = Microglia-specific localisation of a novel calcium binding protein, Iba1 | journal = Brain Res. Mol. Brain Res. | volume = 57 | issue = 1 | pages = 1–9 |date=June 1998 | pmid = 9630473 | doi = 10.1016/s0169-328x(98)00040-0}}
5. ^{{cite journal | vauthors = Utans U, Arceci RJ, Yamashita Y, Russell ME | title = Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic rejection | journal = J. Clin. Invest. | volume = 95 | issue = 6 | pages = 2954–62 |date=June 1995 | pmid = 7769138 | pmc = 295984 | doi = 10.1172/JCI118003 }}
6. ^{{cite journal | vauthors = Autieri MV, Carbone C, Mu A | title = Expression of allograft inflammatory factor-1 is a marker of activated human vascular smooth muscle cells and arterial injury | journal = Arterioscler. Thromb. Vasc. Biol. | volume = 20 | issue = 7 | pages = 1737–44 |date=July 2000 | pmid = 10894811 | doi = 10.1161/01.ATV.20.7.1737 }}
7. ^{{cite journal | vauthors = Autieri MV, Carbone CM | title = Overexpression of allograft inflammatory factor-1 promotes proliferation of vascular smooth muscle cells by cell cycle deregulation | journal = Arterioscler. Thromb. Vasc. Biol. | volume = 21 | issue = 9 | pages = 1421–6 |date=September 2001 | pmid = 11557666 | doi = 10.1161/hq0901.095566 }}
8. ^¹{{cite journal | vauthors = Tian Y, Jain S, Kelemen SE, Autieri MV | title = AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis | journal = Am. J. Physiol., Cell Physiol. | volume = 296 | issue = 2 | pages = C256–66 |date=February 2009 | pmid = 18787073 | pmc = 2643850 | doi = 10.1152/ajpcell.00325.2008 }}
9. ^{{cite journal | vauthors = Hung AY, Sheng M | title = PDZ domains: structural modules for protein complex assembly | journal = J. Biol. Chem. | volume = 277 | issue = 8 | pages = 5699–702 |date=February 2002 | pmid = 11741967 | doi = 10.1074/jbc.R100065200 }}
10. ^{{cite journal | vauthors = Fukui M, Tanaka M, Toda H, Asano M, Yamazaki M, Hasegawa G, Imai S, Fujinami A, Ohta M, Nakamura N | title = The serum concentration of allograft inflammatory factor-1 is correlated with metabolic parameters in healthy subjects | journal = Metab. Clin. Exp. | volume = 61 | issue = 7 | pages = 1021–5 |date=July 2012 | pmid = 22225958 | doi = 10.1016/j.metabol.2011.12.001 }}
11. ^{{cite journal | vauthors = Fukui M, Tanaka M, Asano M, Yamazaki M, Hasegawa G, Imai S, Fujinami A, Ohta M, Obayashi H, Nakamura N | title = Serum allograft inflammatory factor-1 is a novel marker for diabetic nephropathy | journal = Diabetes Res. Clin. Pract. | volume = 97 | issue = 1 | pages = 146–50 |date=July 2012 | pmid = 22560794 | doi = 10.1016/j.diabres.2012.04.009 }}
12. ^{{cite journal | vauthors = Chen ZW, Ahren B, Ostenson CG, Cintra A, Bergman T, Möller C, Fuxe K, Mutt V, Jörnvall H, Efendic S | title = Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 25 | pages = 13879–84 |date=December 1997 | pmid = 9391121 | pmc = 28401 | doi = 10.1073/pnas.94.25.13879 }}

Gene

Function

Clinical significance

References

External links

Further reading