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 protein that is constitutively produced and secreted in a soluble form by most cell types, with major sites of expression in the lung and liver . The human recombinant form of TIMP-2, expressed in HEK (Human Embryonic Kidney) cells, is produced from a DNA sequence encoding the mature human TIMP-2 protein sequence . This recombinant form is often used in research due to its high purity and activity.
TIMP-2 functions as a key modulator of ECM degradation during tissue development and remodeling. It inhibits MMPs by binding to their active sites, thereby preventing the breakdown of ECM components such as collagen and elastin . TIMP-2 has a greater binding efficiency to MMP-2 compared to other MMPs, and it is also required at low concentrations for the activation of MMP-2 .
In addition to its role in ECM regulation, TIMP-2 can act through MMP-independent mechanisms. For example, it has been shown to inhibit endothelial cell proliferation in vitro, demonstrating anti-angiogenic activities in vivo . This makes TIMP-2 a critical player in processes such as wound healing, inflammation, and cancer progression.
The expression and activity of TIMP-2 are tightly regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational modifications. TIMP-2 is a target gene of the microRNA miR-22, which can modulate its expression . Additionally, the balance between MMPs and TIMPs is crucial for maintaining tissue homeostasis, and altered MMP/TIMP ratios are frequently observed in various diseases .
The human recombinant form of TIMP-2 expressed in HEK cells is widely used in research to study its biological functions and regulatory mechanisms. It is also utilized in assays to investigate the role of MMPs and TIMPs in disease pathogenesis and to develop potential therapeutic strategies targeting ECM degradation and remodeling.