Characterization of SMOC-2, a modular extracellular calcium-binding protein

Vannahme, Christian; Gösling, Silke; Paulsson, Mats; Maurer, Patrik; Hartmann, Ursula

doi:10.1042/bj20030532

Cited by 116 publications

(130 citation statements)

References 47 publications

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“…10 SMOC2 is a glycoprotein with a calcium-dependent conformation and has been shown to be expressed in many human tissues. 11 In summary, we have replicated our original finding 6 of association between microsatellite markers at 6q27 and 10p15 with renal failure in an independent cohort of Caucasian individuals. Further informative studies in these chromosomal regions are required to enhance our knowledge and understanding of chronic kidney disease.…”

supporting

confidence: 78%

Association of microsatellite markers on chromosomes 6q27 region and 10p15 region with end-stage renal disease in a UK renal transplant population

et al. 2009

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supporting

confidence: 78%

Association of microsatellite markers on chromosomes 6q27 region and 10p15 region with end-stage renal disease in a UK renal transplant population

et al. 2009

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“…A synthetic peptide sequence (C-YPTLWTEQVKSRQNK) corresponding to the SMOC-2-specific domain (27) was conjugated to KLH: keyhole limpet hemocyanin and used for immunizations.…”

Section: Methodsmentioning

confidence: 99%

“…These SPARC-related proteins include SC1/ Hevin/QR1 (21)(22)(23), Testican (24), tsc36/FRP (25), and the recently-described SMOC-2 (secreted modular calcium-binding protein)/SMAP2 (26). SMOC-2 is expressed in nearly all tissues, with the highest expression found in the heart, muscle tissue, spleen, and ovary (27), but no function has been assigned to this protein. To date, the only clinically relevant role described for SMOC-2 is in the rat carotid artery of accelerated atherosclerotic lesion formation, which demonstrated an upregulation of SMOC-2 mRNA in response to injury (26).…”

mentioning

confidence: 99%

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

Rocnik

Liu

Sato

et al. 2006

Journal of Biological Chemistry

106

109

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SMOC-2 is a novel member of the SPARC family of matricellular proteins. The purpose of this study was to determine whether SMOC-2 can modulate angiogenic growth factor activity and angiogenesis. SMOC-2 was localized in the extracellular periphery of cultured human umbilical vein endothelial cells (HUVECs). Ectopically expressed SMOC-2 was also secreted into the tissue culture medium. In microarray profiling experiments, a recombinant SMOC-2 adenovirus induced the expression of transcripts required for cell cycle progression in HUVECs. Consistent with a growth-stimulatory role for SMOC-2, its overexpression stimulated DNA synthesis in a dosedependent manner. Overexpressed SMOC-2 also synergized with vascular endothelial growth factor or with basic fibroblast growth factor to stimulate DNA synthesis. Ectopically expressed SMOC-2 stimulated formation of network-like structures as determined by in vitro matrigel angiogenesis assays. Fetal calf serum enhanced the stimulatory effect of overexpressed SMOC-2 in this assay. Conversely, small interference RNA directed toward SMOC-2 inhibited network formation and proliferation. The angiogenic activity of SMOC-2 was also examined in experimental mice by subdermal implantation of Matrigel plugs containing SMOC-2 adenovirus. SMOC-2 adenovirus induced a 3-fold increase in the number of cells invading Matrigel plugs when compared with a control adenoviral vector. Basic fibroblast growth factor and SMOC-2 elicited a synergistic effect on cell invasion. Taken together, our results demonstrate that SMOC-2 is a novel angiogenic factor that potentiates angiogenic effects of growth factors.

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“…SMOC2 encodes an EF-hand calciumbinding domain, two thymoglobulin-like domains, a follistatinlike domain, and a novel domain without known homologs (25). The thymoglobulin domains bind and act as inhibitors to different proteases, such as serine and cysteine proteases (38,39).…”

Section: Discussionmentioning

confidence: 99%

“…The thymoglobulin type-1 domains might also act as inhibitors of several proteases. The SMOC2 gene has been cloned and characterized (25). The protein was reported to be expressed in the lung and in the aorta, and the mRNA has been reported to be up-regulated during neointima formation in a rat balloon injury model (24), which suggests that SMOC2 may play an important role in lesion growth.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Secreted Modular Calcium-binding Protein 2 Haplotypes Are Associated with Pulmonary Function

Wilk

Herbert²,

Shoemaker³

et al. 2007

Am J Respir Crit Care Med

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Rationale: Previously reported linkage to FEV 1 (LOD score ϭ 5.0) on 6q27 in the Framingham Heart Study (FHS) led us to explore a candidate gene, SMOC2, at 168.6 Mb. Objectives: We tested association between SMOC2 polymorphisms and FEV 1 and FVC in unrelated FHS participants. Methods: Twenty single-nucleotide polymorphisms (SNPs) around SMOC2 were genotyped in 1,734 subjects. Measurements and Main Results: SNP data were analyzed using multiple linear regression models incorporating sex, age, body mass index, height, and smoking history as covariates, and analyses were repeated within strata of ever-and never-smokers. The minor allele of SNP rs1402 was associated with higher mean FEV 1 (p ϭ 0.003) and FVC (p ϭ 0.02) measures. In never-smoking subjects, association with higher measures was observed with the minor allele of rs747995 (FEV 1 , p ϭ 0.0006; FVC, p ϭ 0.0008). These two SNPs lie in different haplotype blocks and reside in intron 4 of SMOC2. Haplotype analysis revealed a common G-T haplotype (rs747995-rs1402) with 77% frequency in never-smoking FHS subjects. The G-T haplotype was associated with reduction of 126 ml for FEV 1 (p ϭ 0.0002) and 157 ml for FVC (p ϭ 0.0002). The G-T haplotype was similarly associated in a set of never-smoking subjects from the Family Heart Study (FEV 1 , p ϭ 0.03; FVC, p ϭ 0.03). Conclusions:The replication of the association in two populations supports the possibility that SMOC2 might play an important role in the determination of FEV 1 and FVC.Keywords: FEV 1 ; FVC; genetics; single-nucleotide polymorphismThe observation that pulmonary diseases cluster in families (1, 2) and the substantial heritability of spirometric pulmonary function measures demonstrated in population-based samples (3-10) support the hypothesis that genetic factors influence both variability in pulmonary function and risk of chronic obstructive pulmonary disease (COPD). The spirometric measurements of FEV 1 , FVC, and FEV 1 /FVC are estimated to be between 15 and 60% heritable in population-based samples (8, 10). Familial factors may influence lung size during development, as well as affect the response to environmental toxins such as cigarette smoke.Today, ␣ 1 -antitrypsin deficiency is the only proven genetic determinant of COPD (11-16). The homozygous deficiency of the serine protease inhibitor ␣ 1 -antitrypsin is associated with early-onset emphysema in smokers in their fourth decade of life and nonsmokers in their fifth decade (17) and accounts for less What This Study Adds to the FieldThe study provides evidence for the implication of yet another gene, SMOC2, in lung function. SMOC2 was found to affect FEV 1 and FVC in two different populations, the NHLBI Framingham Heart Study and the NHLBI Family Heart Study.than 2% of all COPD (18). The heterozygous form of the mutation has been inconsistently associated with an increased risk of COPD. Mutations in alleles of ␣ 1 -antichymotrypsin, a highly homologous protease inhibitor (19), have also been associated with obstructive lung disease in case-contr...

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Characterization of SMOC-2, a modular extracellular calcium-binding protein

Cited by 116 publications

References 47 publications

Association of microsatellite markers on chromosomes 6q27 region and 10p15 region with end-stage renal disease in a UK renal transplant population

Association of microsatellite markers on chromosomes 6q27 region and 10p15 region with end-stage renal disease in a UK renal transplant population

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

Secreted Modular Calcium-binding Protein 2 Haplotypes Are Associated with Pulmonary Function

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