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.
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.