|CSC-DC000258||Panoply™ Human ADAMTS2 Knockdown Stable Cell Line||Inquiry|
|CSC-SC000258||Panoply™ Human ADAMTS2 Over-expressing Stable Cell Line||Inquiry|
|CDCB190306||Rabbit ADAMTS2 ORF clone (XM_008274971.1)||Inquiry|
|CDCR024646||Human ADAMTS2 ORF clone (NM_014244.4)||Inquiry|
|CDCR024648||Mouse Adamts2 ORF clone (NM_175643.2)||Inquiry|
|CDCR306942||Human ADAMTS2 ORF Clone(NM_021599.2)||Inquiry|
|CDCR377268||Rat Adamts2 ORF Clone(NM_001137622.1)||Inquiry|
|CDFR010265||Rat Adamts2 cDNA Clone(NM_001137622.1)||Inquiry|
|MiUTR1M-01203||ADAMTS2 miRNA 3'UTR clone||Inquiry|
|MiUTR4H-TG00146||ADAMTS2 miRNA 3'UTR clone||Inquiry|
A disintegrin and metalloproteinase with thrombospondin motifs 2 is abbreviated as ADAMTS2. ADAMTS2 was identified as a procollagen I N-protease, a neutral Ca2+ -dependent protease that specifically cleaves type I and type II collagen. The enzyme is located on the long arm at the end of chromosome 5. As early as 1971, enzyme activity was first detected in extracts of normal calf tissue. Proteins isolated from cowhide having a molecular weight of approximately 110 kDa are often found in multimeric complexes. It has mainly been studied for its involvement in dermatosparaxis in cattle, sheep and human type VIIC Ellers syndrome, both connective tissue skin diseases.
The Structure of ADAMTS2
The full-length human pro-ADAMTS2 has a molecular size of 150 kDa. It shares a typical domain structure with other family members, including a 36 amino acid signal peptide, a prodomain, a metalloproteinase domain with a Zn 2+ binding site, followed by Met-turn, a clone feature of the metal peptidase MB. Disintegrants - like domains contains RGD sequences, potential integrin binding sites. ADAMTS2 is released from the enzyme latency by cleavage at the possible two consensus sequence sites, RTRR and RRRMRR, which are known to be specific for mammalian Bacillus subtilis proteins such as furin.
ADAMTS2 mRNA is expressed at high levels in tissues rich in type I collagen (such as skin, bone, tendons, and aorta) and is expressed in trace amounts in the brain and thymus. Consistent with this observation, the enzyme activity was also parallel to the mRNA expression of ADAMTS2. ADAMTS2 has been shown to exist in two forms: a long form very similar to bovine enzymes and a short form of the entire C-terminal region lacking protein, thus most TSR repeats and glycosylation sites. In addition, ADAMTS2 is also regulated by transcriptional levels of TGF-β1, which induces an 8-fold increase in ADAMTS2 mRNA levels in MG-63 human osteosarcoma cells in a dose- and time-dependent manner without affecting RNA stability.
The Function of ADAMTS2
Wang X et al. observed a significant increase in ADAMTS2 expression in the heart of human dilated cardiomyopathy, a pressure overload-induced mouse cardiac hypertrophy model, and angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Further testing of the regulatory role of ADAMTS2 in transgenic mouse models revealed that the degree of cardiac hypertrophy in ADAMTS2 knockout (ADAMTS2-KO) mice were exaggerated. Transgenic (TG) mice that overexpress cardiomyocyte-specific ADAMTS2 are relatively few. It was further confirmed that ADAMTS2-mediated cardioprotection is associated with dephosphorylation of focal adhesion kinase (FAK) and inactivation of PI3K (phosphoinositide 3-kinase) / AKT (protein kinase B).
Studies by Dupont et al. showed that ADAMTS2-Adamts14-deficient mice surprisingly showed epidermal lesions that appeared in 2-month-old males and later appeared in some females and then rapidly deteriorated. Immunohistological evaluation of skin sections surrounding the lesion revealed thickening of the epidermis, the excessive cell in the dermis, and extensive infiltration of immune cells. This indicates that in mice lacking ADAMTS2, spontaneous allergic dermatitis is caused by immune disorders.
Abnormal fibrous hyperplasia (FD) is a kind of fiber. Bone tissue is like hyperplasia. It belongs to bone fibrous tissue hyperplasia but is not a form of cancer. Zhou et al. showed that ADAMTS2 expression was significantly up-regulated in FD compared to normal bone tissue, although there was no significant correlation between ADAMTS2 expression and clinicopathological features. Overexpression of ADAMTS2 in FD was verified as a potential biomarker. These findings suggest that changes in the ADAMTS2 gene may contribute to the development and progression of FD and provide new strategies for its early diagnosis and targeting.
ADAMTS2 and Cancer
Mixed phenotypic acute leukemia (MPAL) includes acute leukemia, which has blasts expressing antigens of more than one lineage, with no evidence of definitive myeloid or lymphoid lineage differentiation. Tota, G.'s study describes a case of T/My MPAL NOS whose complex rearrangement involves chromosomes 5 and 14, resulting in overexpression of the ADAM metallopeptidase and thrombospondin type 1 motif 2 (ADAMTS2) genes. The realization of hematology and cytogenetic responses is associated with normal ADAMTS2 gene expression, comparable to healthy controls.
Figure 1. Schematic representation of the antitumor effects mediated by ADAMTS metalloproteases. (Cal S., et al. 2015)
Cal S et al. summarized the anti-tumor mechanism of ADAMTS metalloproteases and described the role of various metalloproteases including ADAMTS2 in tumorigenesis. Alper et al. demonstrated that interleukin-6 (IL-6) increases ADAMTS-2 and ADAMTS-3 mRNA and protein levels in different osteosarcoma cell lines, MG-63 and Saos-2. IL-6 also increases transcriptional activation of the ADAMTS-2 gene promoter. Studies on pathway inhibition have shown that up-regulation of ADAMTS-2 by IL-6 is mediated by the JNK pathway.
ADAMTS2 and Angiogenesis
ADAMTS2 shows the presence of a CSCTCG motif in its TSR repeat. It has been previously shown that the second TSR domain of TSP-1 inhibits angiogenesis by this motif, thus indicating that ADAMTS2 may also be involved in angiogenesis. The domain and sequence similarity between ADAMTS2 and other anti-angiogenic family members such as ADAMTS1 and ADAMTS8 also indicate possible roles in angiogenesis.
The role of ADAMTS2 in angiogenesis was investigated. Studies have shown that ADAMTS2 inhibits VEGF-stimulated EC proliferation, including human microvascular endothelial cells (HMVEC) and human umbilical vein endothelial cells (HUVEC). This effect shows specificity for EC because the proliferation of smooth muscle cells or fibroblasts is not affected. In addition, ADAMTS2 was also shown to induce apoptosis and prevent the formation of capillary-like structures in HUVECs. Furthermore, it prevents the assembly of embryonic stem cells into vascular structures in embryoid bodies after VEGF stimulation.
The study used a choroidal neovascular model to significantly increase neovascularization in ADAMTS2 knockout mice compared to wild-type animals. Furthermore, HEK293-EBNA cells overexpressing ADAMTS2 significantly reduced tumor growth when transplanted subcutaneously into nude mice. A dense vascular network was observed in the parental tumor, while the tumor overexpressing ADAMTS2 was white with many necrotic areas. Similar results were obtained using a catalytically inactive form of the protein, albeit to a lesser extent, indicating that the catalytic activity of the protein is not necessary for its anti-angiogenic function. The expression of ADAMTS2 in various human cancers was analyzed and it was analyzed whether the vascularization status of these cancers was affected by members of the ADAMTS family. Therefore, ADAMTS2 inhibits tumor growth by inhibiting angiogenesis.
Our promise to you:
Guaranteed product quality, expert customer support.
Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.