The proteins encoded by this gene family are natural inhibitors of thematrix metalloproteinases (MMP), a group ofpeptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation ofendothelial cells. As a result, the encoded protein may be critical to the maintenance of tissuehomeostasis by suppressing the proliferation of quiescent tissues in response toangiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix.[5] TIMP2 functions as both an MMP inhibitor and an activator. TIMPs inhibit active MMPs, but different TIMPs inhibit different MMPs better than others. For example, TIMP-1 inhibits MMP-7, MMP-9, MMP-1 and MMP-3 better than TIMP-2, and TIMP-2 inhibits MMP-2 more effectively than other TIMPs.[6]
In melanocytic cells TIMP2 gene expression may be regulated byMITF.[7]
A recent discovery is that TIMP2 plays an important role inhippocampal function and cognitive function. It plays a critical role in the benefit conferred to old mice when given humanumbilical cord blood.[8][9] Its role in hippocampal function was later described to be related to its interactions with theextracellular matrix to regulateneurogenesis anddendritic spines plasticity.[10]
Stetler-Stevenson WG, Seo DW (March 2005). "TIMP-2: an endogenous inhibitor of angiogenesis".Trends in Molecular Medicine.11 (3):97–103.doi:10.1016/j.molmed.2005.01.007.PMID15760767.
