• Clinical and Experimental Pediatrics
• /
• v.53 no.3
• /
• pp.428-431
• /
• 2010

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.

• Bulletin of the Korean Chemical Society
• /
• v.33 no.9
• /
• pp.2907-2909
• /
• 2012

A disintegrin and metalloprotease with thrombospondin domains (ADAMTS) are a member of peptidase and involved in processing of von Willebrand factor as well as cleavage of aggrecan, versican, brevican and neurocan. Among 19 subfamilies of human ADAMTS, ADAMTS-4 is a zinc-binding metalloprotease and is a famous therapeutic target for arthritis. It has been reported that a flavonoid luteolin shows inhibitory activity against ADMATS-4. In this study, we verified that luteolin is a potent inhibitor of ADAMTS-4 and probed the molecular basis of its action. On the basis of a docking study, we proposed a binding model between luteolin and ADAMTS-4 in which 3',4'-dihydroxyl groups in luteolin formed hydrogen bonding with ADMATS-4 and these interactions are important for its inhibitory activity against ADAMTS-4.

• International Journal of Oral Biology
• /
• v.31 no.3
• /
• pp.93-98
• /
• 2006

Biosynthetic processing of fibrillar procollagens is essential for producing mature collagen monomers that polymerize into fibrils by a self-assembly process. The metalloproteinase ADAMTS-2 is the major enzyme that processes the N-propeptide of type I procollagen in the skin and also of type II and type III procollagens. Mutations in the ADAMTS-2 gene cause dermatospraxis in animals and Ehlers-Danlos syndrome VIIC in humans, both of which are characterized by the accumulation of type I pN-collagen and the formation of abnormal collagen fibrils in the skin. Despite its importance in procollagen processing, little is known about the regulation of ADAMTS-2 expression. Here, we demonstrate that ADAMTS-2 can be regulated by 1,25-dihydroxyvitamin D3, an inducer of type I procollagen synthesis. This steroid hormone induced ADAMTS-2 mRNA ${\sim}3-fold$ in MG-63 human osteosarcoma cells and MC3T3-E1 murine osteoblastic cells. This induction was dose- and time-dependent in MG-63 cells. In contrast, secreted ADAMTS-2 protein was increased only 1.4-fold with 1,25-dihydroxyvitamin D3. Finally, 1,25-dihydroxyvitamin D3 in the presence of ascorbate increased levels of secreted ADAMTS-2 1.9-fold over ascorbate treatment alone, which did not appreciably change ADAMTS-2 expression. These data indicate that the regulation of ADAMTS-2 is coupled with the synthesis of type I procollagen through 1,25-dihydroxyvitamin D3 signaling and may involve translational or posttranslational control.

• Asian-Australasian Journal of Animal Sciences
• /
• v.31 no.8
• /
• pp.1366-1372
• /
• 2018

Objective: A disintegrin and metallopeptidase with thrombospondin motifs type 8 (ADAMTS8) is crucial for diverse physiological processes, such as inflammation, tissue morphogenesis, and tumorigenesis. The chicken ADAMTS8 (chADAMTS8) gene was differentially expressed in the kidney following exposure to different calcium concentrations, suggesting a pathological role of this protein in metabolic diseases. We aimed to examine the molecular characteristics of chADAMTS8 and analyze the gene-expression differences in response to toll-like receptor 3 (TLR3) stimulation. Methods: The ADAMTS8 mRNA and amino acid sequences of various species (chicken, duck, cow, mouse, rat, human, chimpanzee, pig, and horse) were retrieved from the Ensembl database and subjected to bioinformatics analyses. Reverse-transcription polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR) experiments were performed with various chicken tissues and the chicken fibroblast DF-1 cell line, which was stimulated with polyinosinic-polycytidylic acid (poly[I:C]; a TLR3 ligand). Results: The chADAMTS8 gene was predicted to contain three thrombospondin type 1 (TSP1) domains, whose amino acid sequences shared homology among the different species, whereas sequences outside the TSP1 domains (especially the amino-terminal region) were very dif­ferent. Phylogenetic analysis revealed that chADAMTS8 is evolutionarily clustered in the same clade with that of the duck. chADAMTS8 mRNA was broadly expressed in chicken tissues, and the expression was significantly up-regulated in the DF-1 cells in response to poly(I:C) stimulation (p<0.05). These results showed that chADAMTS8 may be a target gene for TLR3 signaling. Conclusion: In this report, the genetic information of chADAMTS8 gene, its expression in chicken tissues, and chicken DF-1 cells under the stimulation of TLR3 were shown. The result suggests that chADAMTS8 expression may be induced by viral infection and correlated with TLR3-mediated signaling pathway. Further study of the function of chADAMTS8 during TLR3-dependent inflammation (which represents RNA viral infection) is needed and it will also be important to examine the molecular mechanisms during different regulation, depending on innate immune receptor activation.

• Childhood Kidney Diseases
• /
• v.10 no.2
• /
• pp.109-118
• /
• 2006

Purpose : HUS usually occurs in children after infection with shiga toxin-producing microorganism(D＋HUS). In contrast, non-postdiarrheal(D-) HUS occurs at any age and has a high rate of relapse and a poor prognosis. The clinical presentation of D-HUS is similar to that of thrombotic thrombocytopenic purpura(TTP). Recently severe deficiencies of ADAMTS13 were reported not only in TTP and D- HUS but also in D+ HUS during their acute phase. The purpose of the study is to evaluate the plasma ADAMTS13 activity in D＋ and D-HUS. Methods : Nineteen children with HUS(D＋ HUS 12 and D- HUS 7) were enrolled. The assays of plasma ADAMTS13 activity were performed during the acute stage in the D＋ HUS and at various stages of relapsing courses in the D- HUS patients by multimer assay, based on electrophoresis. Results : The median plasma activity of ADAMTS13 in D＋ HUS and D- HUS were 80.9%(37.8-132.4%) and 53.9%(1.0-94.1%), respectively, which were not statistically significantly different from control(86.4%, 34.2-112.3%)(P>0.05). One boy with D- HUS had severe deficiency of ADAMTS13(1.0%). His platelet count was normalized temporarily by fresh frozen plasma infusion. Conclusion : We have demonstrated that there is no significant difference of the plasma ADAMTS13 activity between D＋ HUS, D- HUS and control. We detected severe deficiency of ADAMTS13 in one boy who presented with relapsing episodes of D- HUS. ADAMTS13 deficiency should be considered in the subgroup of D- HUS especially with early onset and recurrent courses. Plasma therapy can be beneficial in this subgroup.

• BMB Reports
• /
• v.46 no.3
• /
• pp.139-150
• /
• 2013

The ADAM and ADAMTS families, also called adamalysins belong to an important group of extracellular matrix proteins. The ADAMs family belong to both the transmembrane and secreted proteins, while ADAMTS family only contains secreted forms. Adamalysins play an important role in the cell phenotype regulation via their activities in signaling pathways, cell adhesion and migration. The human proteome contains 21 ADAM, and 19 ADAMTS proteins, which are involved in extracellular matrix remodeling, shedding of various substrates such as: adhesion ligands, growth factors, their receptors and diverse cytokines. Recent studies provide evidence that adamalysins play a crucial role in colorectal cancer (CRC) etiopathogenesis. It seems possible that adamalysins might be used as CRC prediction markers or potential pharmaceutical targets.

• Clinical and Experimental Reproductive Medicine
• /
• v.41 no.3
• /
• pp.120-124
• /
• 2014

Objective: The aim of the present study was to examine whether interactions between polymorphisms in the thyroglobulin and ADAM metallopeptidase with thrombospondin type 1 motif, 16 (ADAMTS16) genes are associated with the development of premature ovarian failure (POF). Methods: A total of 75 patients with POF and 196 controls were involved in this study. We used a GoldenGate assay to genotype single nucleotide polymorphisms (SNPs). Logistic regression analysis was performed to identify POF-associated polymorphisms and synergistic interactions between polymorphisms in the thyroglobulin and ADAMTS16 genes. Results: Single gene analyses using logistic regression analysis showed no significant association between polymorphisms in the two genes and POF. In the results from interaction analyses, we found seven synergistic interactions between the polymorphisms in thyroglobulin and ADAMTS16, although there was no combination showing p-values lower than the significant threshold using the Bonferroni correction. When the AG genotype was present at the rs853326 missense SNP, the A and G alleles at the tagging SNPs rs16875268 and rs13168665 showed significant interactions (odds ratios=5.318 and 16.2 respectively; 95% confidence intervals, 1.64-17.28 and 2.08-126.4; p=0.0054 and 0.0079). Conclusion: Synergistic interactions between polymorphisms in the thyroglobulin and ADAMTS16 genes were associated with an increased risk of POF development in Korean women.

• Asian-Australasian Journal of Animal Sciences
• /
• v.21 no.7
• /
• pp.917-922
• /
• 2008

A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif (ADAMTS1) plays a critical role in follicular rupture and represents a major advance in the proteolytic events that control ovulation. In this study, a 9,026-bp DNA sequence containing the full coding region, all 8 introns and part of the 5'and 3' untranslated region of the porcine ADAMTS1 gene was obtained. Analysis of the ADAMTS1 gene using the porcine radiation hybrid panel indicated that pig ADAMTS1 is closely linkage with microsatellite marker S0215, located on SSC13q49. The open reading frame of its cDNA covered 2,844 bp and encoded 947 amino acids. The coding region of porcine ADAMTS1 as determined by sequence alignments shared 85% and 81% identity with human and mouse cDNAs, respectively. The deduced protein contained 947 amino acids showing 85% sequence similarity both to the human and mouse proteins, respectively. Comparative sequencing of three pig breeds revealed one single nucleotide polymorphism (SNP) within exon 7 of which a G-C substitution at position 6006 changes a codon for arginine into a codon for proline. The substitution was situated within a PvuII recognition site and developed as a PCR-RFLP marker for further use in population variation investigations and association analysis with litter size. Allele frequencies of this SNP were investigated in seven pig breeds/lines. An association analysis in a new Qingping female line suggested that different ADAMTS1 genotypes have significant differences in litter size (p<0.01).

• Development and Reproduction
• /
• v.8 no.2
• /
• pp.99-111
• /
• 2004

The present study aimed to investigate whether the expression of ADAM-8, 9, 10, 12, 15, 17 and ADAMTS-1 genes is controlled by ovarian steroid hormones. Ovariectomized mice were injected with 17 ${\beta}$-estradiol ($E_2$), progesterone ($P_4$, or $E_2+P_4$. Uterine tissues were processed for RT-PCR and immunoblotting. The results of RT-PCR showed that administration of $E_2$ increases the level of ADAM-8, 12 and ADAM17 expression compared to $P_4$ or control group. In contrast, administration of $P_4$ markedly stimulated the expression of ADAM-9, 10, 15 and ADAMTS-1, whereas $E_2$ did not. Immunoblotting analysis using anti-mouse ADAM polyclonal antibodies demonstrated that $E_2$ alone or $E_2+P_4$ treatment results in the strong expression of ADAM-8, 12 and ADAM17 proteins but $P_4$ alone or control group gave weak expression. In contrast, $P_4$ alone or $E_2$ plus $P_4$ treatment increased the expression level of ADAM-9, 10, 15 and DAMTS-1 proteins. $E_2$ alone or control group did not increase the expression. These results indicate that expression of ADAM-8, 12 and ADAM17 genes is upregulated by $E_2$ and that of ADAM-9, 10, 15 and ADAMTS-1 gene is upregulated by $P_4$.

• Clinical and Experimental Reproductive Medicine
• /
• v.32 no.1
• /
• pp.33-46
• /
• 2005

연구목적: ADAMs은 metalloprotease/disintegrin domain을 가진 transmemebrane glycoprotein으로써 지금까지 30개 이상의 ADAM 및 10개 이상의 ADAMTS가 알려져 있다. 이들의 기능은 포유동물의 수정 시 sperm-egg binding과 fusion, myoblast fusion, integrin과의 결합 등에 직접 관여하거나, TNF-alpha 등의 생체신호전달물질이 세포로부터 분비될 때에 이들의 구조를 변화시켜 활성화시키는 효소작용, 그리고 dendritic cell differentiation 등에 관여하는 것으로 알려져 있다. 그러나 자궁내막 조직에서의 유전자 및 단백질 발현 여부에 관해서는 거의 보고되어 있지 않고 있다. 본 연구에서는 착상 전후 시기의 생쥐 자궁조직에서 ADAM-8, 9, 10, 12, 15, 17 그리고 ADAMTS-1의 유전자가 발현하는 지를 알아보았다. 연구 재료 및 방법: 본 연구에서는 생쥐의 자궁조직을 대상으로 ADAM-8, 9, 10, 12, 15, 17 그리고 ADAMTS-1을 선정하여, 초기 임신 기간에서의 유전자 발현 여부를 조사하였고 이 결과를 바탕으로 자궁조직에서의 이들 유전자들의 생리적인 기능을 규명하고자 하였다. 결 과: 임신한 생쥐 자궁조직에서의 ADAM-8, 9, 10, 12, 15, 17 그리고 ADAMTS-1의 유전자 및 단백질의 발현 양상을 RT-PCR 방법을 이용하여 알아본 결과, 조사된 ADAM 종류와 임신 날짜별로 다르게 나타났다. ADAM-8의 유전자 전사체는 임신 1일째 매우 강하게 발현되었으나 임신 3일째로 진행되면서 감소하다가 이후 다시 임신 5일째가 되면서 증가하는 양상을 보였다. ADAM-9, 10, 17 그리고 ADAMTS-1의 경우는 임신 1일째에서 5일째까지 유전자의 발현 양상이 크게 변하지 않았고 ADAM-12와 ADAM-15의 유전자 전사체는 임신 1일에서 5일로 진행되면서 현저하게 증가되는 양상을 보였다. 이후 임신 6일에서 8일에서는 생쥐 배아가 착상된 부위와 비 착상부위로 나누어 유전자의 발현 양상을 관찰한 결과, 조사된 ADAM 모두 비착상 부위보다 착상부위에서 유전자 전사체의 발현이 크게 증가되는 것으로 나타났다. 결 론: 이상의 결과로 미루어 ADAM 유전자는 임신초기 착상과정과 임신 단계에 따른 자궁의 조직 재구성에 중요한 역할을 할 것으로 생각된다.