Identifiers
HUGO:TIMP3
Maps_Modules
MODULE:EFFECTOR_INHIBITION MODULE:TUMOR_GROWTH MODULE:MATRIX_REMODELLING
References
MACROPHAGE
CASCADE:IL4
PMID:22880008
Classical activation of macrophages derived in vitro from un-fractionated CD16(+/-) or negatively-selected CD16(-) macrophages up-regulated MMP-1, -3, -7, -10, -12, -14 and -25 and decreased TIMP-3 steady-state mRNA levels.
By contrast, alternative activation decreased MMP-2, -8 and -19 but increased MMP -11, -12, -25 and TIMP-3 steady-state mRNA levels. Up-regulation of MMPs during classical activation depended on mitogen activated protein kinases, phosphoinositide-3-kinase and inhibitor of κB kinase-2. Effects of interferonγ depended on janus kinase-2.
PMID:25171061, PMID:26707830
TIMP3 is a dominant negative regulator of angiogenesis
TIMP-3 expression in tumor microenvironment suggests a favorable prognosis for HCC patients.
PMID:25807548
Among the TIMP family, TIMP3 is unique in that it is tightly bound to the extracellular matrix via heparan sulfate and it has the most broad protease-inhibition profile which in addition to MMPs includes many ADAMs (a disintegrin and metalloproteinase). Specifically, TIMP3 is the sole inhibitor of ADAM17, also known as tumor necrosis factor alpha (TNF) converting enzyme (TACE)
→ TIMP3@INNATE_IMMUNE_CELL_Cytosol
→ MATRIX_REMODELLING@default