Genomes and Genes
Gene Symbol: Ahsg
Alias: alpha-2-HS-glycoprotein, countertrypin, fetuin-A
- Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, et al. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest. 2003;112:357-66 pubmed..Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level...
- Szweras M, Liu D, Partridge E, Pawling J, Sukhu B, Clokie C, et al. alpha 2-HS glycoprotein/fetuin, a transforming growth factor-beta/bone morphogenetic protein antagonist, regulates postnatal bone growth and remodeling. J Biol Chem. 2002;277:19991-7 pubmed..Therefore, we examined bone growth and remodeling phenotypes in ASHG-deficient mice. The skeletal structure of Ahsg(-/-) mice appeared normal at birth, but abnormalities were observed in adult Ahsg(-/-) mice...
- Demetriou M, Binkert C, Sukhu B, Tenenbaum H, Dennis J. Fetuin/alpha2-HS glycoprotein is a transforming growth factor-beta type II receptor mimic and cytokine antagonist. J Biol Chem. 1996;271:12755-61 pubmed..In summary, these experiments define the TRH1 peptide loop as a cytokine-binding domain in both TbetaRII and fetuin and suggest that fetuin is a natural antagonist of TGF-beta and BMP activities. ..
- Schinke T, Amendt C, Trindl A, Pöschke O, Muller Esterl W, Jahnen Dechent W. The serum protein alpha2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem. 1996;271:20789-96 pubmed..Fetuins account for roughly half of the capacity of serum to inhibit salt precipitation. We propose that fetuins inhibit phase separation in serum and modulate apatite formation during mineralization. ..
- Jahnen Dechent W, Schinke T, Trindl A, Muller Esterl W, Sablitzky F, Kaiser S, et al. Cloning and targeted deletion of the mouse fetuin gene. J Biol Chem. 1997;272:31496-503 pubmed..These results corroborate a role for fetuin in serum calcium homeostasis. The fact that generalized ectopic calcification did not occur in fetuin-deficient mice proves that additional inhibitors of phase separation exist in serum. ..
- Jahnen Dechent W, Heiss A, Schafer C, Ketteler M. Fetuin-A regulation of calcified matrix metabolism. Circ Res. 2011;108:1494-509 pubmed publisher..Fetuin-A deficiency is associated with soft tissue calcification in mice and humans. ..
- Westenfeld R, Schafer C, Smeets R, Brandenburg V, Floege J, Ketteler M, et al. Fetuin-A (AHSG) prevents extraosseous calcification induced by uraemia and phosphate challenge in mice. Nephrol Dial Transplant. 2007;22:1537-46 pubmed..Calcification was preceded by the local induction of osteopontin, a marker for osteoblast-like cell differentiation. Fetuin-A deficiency, CKD and high phosphate diet act synergistically in the pathogenesis of extraosseous calcification. ..
- Heiss A, DuChesne A, Denecke B, Grötzinger J, Yamamoto K, Renne T, et al. Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem. 2003;278:13333-41 pubmedGenetic evidence from mutant mice suggests that alpha(2)-HS glycoprotein/fetuin-A (Ahsg) is a systemic inhibitor of precipitation of basic calcium phosphate preventing unwanted calcification...
- Bochkis I, Schug J, Ye D, Kurinna S, Stratton S, Barton M, et al. Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2. PLoS Genet. 2012;8:e1002770 pubmed publisher..Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. ..
- Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, et al. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med. 2012;18:1279-85 pubmed publisher..FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-..
- Kundranda M, Henderson M, Carter K, Gorden L, Binhazim A, Ray S, et al. The serum glycoprotein fetuin-A promotes Lewis lung carcinoma tumorigenesis via adhesive-dependent and adhesive-independent mechanisms. Cancer Res. 2005;65:499-506 pubmed..These studies support the role of fetuin-A as a major growth promoter in serum that can influence tumor establishment and growth. ..
- Jethwaney D, Lepore T, Hassan S, Mello K, Rangarajan R, Jahnen Dechent W, et al. Fetuin-A, a hepatocyte-specific protein that binds Plasmodium berghei thrombospondin-related adhesive protein: a potential role in infectivity. Infect Immun. 2005;73:5883-91 pubmed..These data demonstrate that the extracellular region of TRAP interacts with fetuin-A on hepatocyte membranes and that this interaction enhances the parasite's ability to invade hepatocytes. ..
- Brylka L, Jahnen Dechent W. The role of fetuin-A in physiological and pathological mineralization. Calcif Tissue Int. 2013;93:355-64 pubmed publisher..Fetuin-A-deficient (Ahsg(-/-)) mice show impaired growth of their long bones and premature growth plate closure...
- Mattinzoli D, Rastaldi M, Ikehata M, Armelloni S, Pignatari C, Giardino L, et al. FGF23-regulated production of Fetuin-A (AHSG) in osteocytes. Bone. 2016;83:35-47 pubmed publisherb>AHSG, a serum glycoprotein with recognized anti-calcification activity, has also been suggested to modulate both bone formation and resorption...
- Ou H, Wu H, Hung H, Yang Y, Wu J, Chang C. Endoplasmic reticulum stress induces the expression of fetuin-A to develop insulin resistance. Endocrinology. 2012;153:2974-84 pubmed publisher..Moreover, ER stress induced by high glucose and palmitate increased the expression of fetuin-A and further contributed to the development of insulin resistance. ..
- Yamamoto K, Sinohara H. Isolation and characterization of mouse countertrypin, a new trypsin inhibitor belonging to the mammalian fetuin family. J Biol Chem. 1993;268:17750-3 pubmedA novel trypsin inhibitor, tentatively named countertrypin, was isolated from mouse plasma in an apparently homogeneous state...
- Wöltje M, Tschöke B, von Bulow V, Westenfeld R, Denecke B, Gräber S, et al. CCAAT enhancer binding protein beta and hepatocyte nuclear factor 3beta are necessary and sufficient to mediate dexamethasone-induced up-regulation of alpha2HS-glycoprotein/fetuin-A gene expression. J Mol Endocrinol. 2006;36:261-77 pubmedAlpha2HS-glycoprotein/fetuin-A (Ahsg) is a serum protein preventing soft tissue calcification. In trauma and inflammation, Ahsg is down-regulated and therefore considered a negative acute phase protein...
- Herrmann M, Schafer C, Heiss A, Gräber S, Kinkeldey A, Büscher A, et al. Clearance of fetuin-A--containing calciprotein particles is mediated by scavenger receptor-A. Circ Res. 2012;111:575-84 pubmed publisher..Biochemical studies showed that fetuin-A is essential for the formation of protein-mineral complexes, called calciprotein particles (CPPs). CPPs must be cleared from circulation to prevent local deposition and pathological calcification...
- Brylka L, Köppert S, Babler A, Kratz B, Denecke B, Yorgan T, et al. Post-weaning epiphysiolysis causes distal femur dysplasia and foreshortened hindlimbs in fetuin-A-deficient mice. PLoS ONE. 2017;12:e0187030 pubmed publisherFetuin-A / α2-Heremans-Schmid-glycoprotein (gene name Ahsg) is a systemic inhibitor of ectopic calcification. Due to its high affinity for calcium phosphate, fetuin-A is highly abundant in mineralized bone matrix...
- Harris V, Donelan N, Yan Q, Clark K, Touray A, Rammal M, et al. Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis. Mult Scler. 2013;19:1462-72 pubmed publisher..Our results show that CSF fetuin-A is a biomarker of disease activity and natalizumab response in MS. Neuronal expression of fetuin-A suggests that fetuin-A may play a pathological role in the disease process. ..
- Chatterjee P, Seal S, Mukherjee S, Kundu R, Mukherjee S, Ray S, et al. Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages. J Biol Chem. 2013;288:28324-30 pubmed publisher..Taken together, lipid-induced FetA from adipocytes is an efficient chemokine for macrophage migration and polarization. These findings open a new dimension for understanding obesity-induced inflammation. ..
- Cintron V, Ko M, Chi K, Gross J, Srinivas P, Goustin A, et al. Genetic mapping and functional studies of a natural inhibitor of the insulin receptor tyrosine kinase: the mouse ortholog of human alpha2-HS glycoprotein. Int J Exp Diabetes Res. 2001;1:249-63 pubmed..In this study we report the identification, cloning, and characterization of the mouse Ahsg gene and its function as an IR-TK inhibitor...
- Tsujimura T, Morii E, Nozaki M, Hashimoto K, Moriyama Y, Takebayashi K, et al. Involvement of transcription factor encoded by the mi locus in the expression of c-kit receptor tyrosine kinase in cultured mast cells of mice. Blood. 1996;88:1225-33 pubmed..Thus, the involvement of (+)-MITF in the c-kit transactivation appeared to be specific to the mast cell lineage. ..
- Swallow C, Partridge E, Macmillan J, Tajirian T, DiGuglielmo G, Hay K, et al. alpha2HS-glycoprotein, an antagonist of transforming growth factor beta in vivo, inhibits intestinal tumor progression. Cancer Res. 2004;64:6402-9 pubmed..Here, we show that the serum glycoprotein alpha2-HS-glycoprotein (AHSG) blocks TGF-beta1 binding to cell surface receptors, suppresses TGF-beta signal transduction, and inhibits TGF-beta-..
- Merx M, Schafer C, Westenfeld R, Brandenburg V, Hidajat S, Weber C, et al. Myocardial stiffness, cardiac remodeling, and diastolic dysfunction in calcification-prone fetuin-A-deficient mice. J Am Soc Nephrol. 2005;16:3357-64 pubmed....
- Jochheim A, Cieslak A, Hillemann T, Cantz T, Scharf J, Manns M, et al. Multi-stage analysis of differential gene expression in BALB/C mouse liver development by high-density microarrays. Differentiation. 2003;71:62-72 pubmed..Furthermore, the microarray approach led to the identification of a number of genes, which have not yet been associated with liver organogenesis and maturation. ..
- Zhang P, Fan X, Haichao W. [The expression of fetuin-A and its pathological significance in fulminant hepatic failure in mice]. Zhonghua Gan Zang Bing Za Zhi. 2008;16:440-4 pubmed..01). Fetuin-A expressions were negatively correlated with the liver pathological scores and TNFa levels. In our mouse FHF model, fetuin-A is a possible protective factor for liver damage. ..
- Caballero Hernandez D, Gomez Flores R, Tamez Guerra P, Tamez Guerra R, Rodriguez Padilla C. Role of immunogenic fetuin A on L5178Y-R lymphoma tumorigenesis. Cancer Invest. 2009;27:257-63 pubmed publisher....
- Westenfeld R, Schafer C, Kruger T, Haarmann C, Schurgers L, Reutelingsperger C, et al. Fetuin-A protects against atherosclerotic calcification in CKD. J Am Soc Nephrol. 2009;20:1264-74 pubmed publisher..In conclusion, fetuin-A inhibits pathologic calcification in both the soft tissue and vasculature, even in the setting of atherosclerosis. ..
- Guillory B, Sakwe A, Saria M, Thompson P, Adhiambo C, Koumangoye R, et al. Lack of fetuin-A (alpha2-HS-glycoprotein) reduces mammary tumor incidence and prolongs tumor latency via the transforming growth factor-beta signaling pathway in a mouse model of breast cancer. Am J Pathol. 2010;177:2635-44 pubmed publisher..The data indicate that Fet is a powerful modulator of breast tumorigenesis in this model system and has the potential to modulate breast cancer progression in humans. ..
- Olivier E, Soury E, Ruminy P, Husson A, Parmentier F, Daveau M, et al. Fetuin-B, a second member of the fetuin family in mammals. Biochem J. 2000;350 Pt 2:589-97 pubmed..However, like its fetuin-A counterpart, the fetuin-B mRNA level is down-regulated during the acute phase of experimentally induced inflammation in rat. ..
- Lau W, Liu S, Vaziri N. Chronic kidney disease results in deficiency of ABCC6, the novel inhibitor of vascular calcification. Am J Nephrol. 2014;40:51-5 pubmed publisher..Given the prevalence of arterial medial calcification in CKD, the present study was undertaken to test the hypothesis that CKD may lead to acquired ABCC6 deficiency...
- Piazzon N, Bernet F, Guihard L, Leonhard W, Urfer S, Firsov D, et al. Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression. J Transl Med. 2015;13:103 pubmed publisher..Our findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD. ..
- Liu A, Chen M, Kumar R, Stefanovic Racic M, O Doherty R, Ding Y, et al. Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4. Nat Commun. 2018;9:708 pubmed publisher..Our findings raises important questions about the impact of maternal obesity and endotoxemia to fetal hematopoiesis, as fetal immune precursors are also sensitive to TLR4 signals. ..
- Li W, Zhu S, Li J, Huang Y, Zhou R, Fan X, et al. A hepatic protein, fetuin-A, occupies a protective role in lethal systemic inflammation. PLoS ONE. 2011;6:e16945 pubmed publisher..These experimental data suggest that fetuin-A is protective against lethal systemic inflammation partly by inhibiting active HMGB1 release. ..
- Rittenberg B, Partridge E, Baker G, Clokie C, Zohar R, Dennis J, et al. Regulation of BMP-induced ectopic bone formation by Ahsg. J Orthop Res. 2005;23:653-62 pubmedalpha2-HS-glycoprotein (Ahsg), also known as fetuin is a serum and bone resident glycoprotein, which binds to TGF-beta superfamily members including bone morphogenetic proteins (BMP) and inhibits dexamethasone-induced osteogenesis in bone ..
- Leite Browning M, McCawley L, Jahnen Dechent W, King L, Matrisian L, Ochieng J. Alpha 2-HS glycoprotein (fetuin-A) modulates murine skin tumorigenesis. Int J Oncol. 2004;25:319-24 pubmed..Our results suggest that fetuin-A contributes to early stages of skin tumorigenesis. ..
- Denecke B, Gräber S, Schafer C, Heiss A, Wöltje M, Jahnen Dechent W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J. 2003;376:135-45 pubmed..Therefore fetuin-B may have a function that is partly overlapping, if not identical, with the function of fetuin-A. ..
- Salier J, Chan P, Raguenez G, Zwingman T, Erickson R. Developmentally regulated transcription of the four liver-specific genes for inter-alpha-inhibitor family in mouse. Biochem J. 1993;296 ( Pt 1):85-91 pubmed....
- Seto J, Busse B, Gupta H, Schafer C, Krauss S, Dunlop J, et al. Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice. PLoS ONE. 2012;7:e47338 pubmed publisherThe plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient ..
- Mathews S, Rakhade S, Zhou X, Parker G, Coscina D, Grunberger G. Fetuin-null mice are protected against obesity and insulin resistance associated with aging. Biochem Biophys Res Commun. 2006;350:437-43 pubmedalpha2-HS glycoprotein (AHSG), also known as fetuin-A, inhibits insulin receptor autophosphorylation and tyrosine kinase activity in vitro and in vivo...
- Mathews S, Singh G, Ranalletta M, Cintron V, Qiang X, Goustin A, et al. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes. 2002;51:2450-8 pubmed..The fetuin gene (AHSG) is located on human chromosome 3q27, recently identified as a susceptibility locus for type 2 diabetes and the ..
- Altmann S, Davis H, Yao X, Laverty M, Compton D, Zhu L, et al. The identification of intestinal scavenger receptor class B, type I (SR-BI) by expression cloning and its role in cholesterol absorption. Biochim Biophys Acta. 2002;1580:77-93 pubmed..In contrast studies with SR-B1 knockout mice suggest that SR-B1 is not essential for intestinal cholesterol absorption or the activity of ezetimibe. ..
- Yang F, Chen Z, Bergeron J, Cupples R, Friedrichs W. Human alpha 2-HS-glycoprotein/bovine fetuin homologue in mice: identification and developmental regulation of the gene. Biochim Biophys Acta. 1992;1130:149-56 pubmedHuman alpha 2-HS-glycoprotein (AHSG) is a plasma protein synthesized in liver and selectively concentrated in bone matrix. It has been reported to be involved in bone formation and resorption as well as immune responses...