Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) is a member of the TIMP family, which consists of four endogenous proteins that primarily function to inhibit the activities of matrix metalloproteinases (MMPs). MMPs are a family of enzymes responsible for the degradation of the extracellular matrix (ECM) and play a significant role in various physiological processes, including cell migration, angiogenesis, and tissue remodeling .
TIMP-2 is a secreted, multifunctional protein with a molecular weight of approximately 21 kDa. It was first described in 1989 and shows about 40% amino acid identity with TIMP-1 . TIMP-2 inhibits the active form of MMP-2 and also complexes with the proform of MMP-2 . This inhibition is crucial for maintaining the balance between proteases and antiproteases, which is essential for ECM turnover and cellular environment maintenance .
TIMP-2 plays a vital role in regulating ECM turnover by inhibiting MMP activity. This regulation is important in preventing excessive ECM degradation, which can lead to various pathological conditions. Elevated levels of TIMPs, including TIMP-2, are associated with ECM accumulation and fibrosis, while a loss of TIMP responses can result in enhanced matrix proteolysis .
In addition to its role in inhibiting MMPs, TIMP-2 has been found to have other biological functions. It diminishes growth factor-mediated cell proliferation in vitro and inhibits neoangiogenesis and tumor growth in vivo . These properties make TIMP-2 a potential candidate for further pre-clinical development as a biologic therapy for cancer .
Recombinant human TIMP-2 is produced using DNA sequences encoding the mature human TIMP-2 protein sequence expressed in CHO (Chinese Hamster Ovary) cells . The production process involves optimizing both the TIMP-2 cDNA codon sequence and cell culture conditions to achieve high yields of the protein. A two-step chromatographic process is used to purify the protein, resulting in a product with over 95% purity and minimal processing losses .
Recombinant TIMP-2 can be used as a positive control in enzymatic and other assays . Its ability to inhibit MMP-2 enzymatic activity in a dose-dependent fashion makes it a valuable tool for studying ECM turnover and related processes. Furthermore, TIMP-2’s anti-proliferative and anti-angiogenic properties highlight its potential as a therapeutic agent for cancer treatment .
Future research on TIMP-2 could explore its roles in aging and inflammation processes, as well as its potential applications in other diseases characterized by ECM dysregulation . Understanding the full spectrum of TIMP-2’s biological functions will be crucial for developing targeted therapies that leverage its unique properties.