TIMP metallopeptidase inhibitor 1, also known asTIMP1, atissue inhibitor of metalloproteinases, is a glycoprotein with a molecular weight of 28 kDa.[5] TIMP1 is expressed from several tissues of organisms.
This protein is a member of theTIMP family. Theglycoprotein is a naturalinhibitor of thematrix metalloproteinases (MMPs), a group of peptidases involved in degradation of theextracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promotecell proliferation in a wide range of cell types, and may also have an anti-apoptotic function.
TIMP1 is an inhibitory molecule that regulates matrix metalloproteinases (MMPs), and disintegrin-metalloproteinases (ADAMs and ADAMTSs).[6] In regulating MMPs, TIMP1 plays a crucial role in extracellular matrix (ECM) composition, wound healing,[7] and pregnancy.[8][9][10]
The dysregulated activity of TIMP1 has been implicated in cancer.[11] In pregnancy, TIMP1 plays a regulatory role in the process of implantation, particularly the cytotrophoblast invasion of the uterine endometrium.[12] Additionally, it plays a role in regulating the transcriptional profile of fetal and placental tissues associated with the early stages of pregnancy.[13] Studies attribute this role to a mechanism involving the chromatin structure at the TIMP1 promoter region, implicating new pharmaceutical possibilities for the therapeutic regulation of TIMP1. Accordingly, TIMP1 can be manipulatedin vitro using techniques, like the TIMP1 knock-out.[14][15][16]
Transcription of thisgene is highly inducible in response to manycytokines andhormones. In addition, the expression from some but not all inactiveX chromosomes suggests that this gene inactivation is polymorphic inhumanfemales. This gene is located within intron 6 of thesynapsin I gene and is transcribed in the opposite direction.[17]
In adrenocortical cells the trophic hormone ACTH induces expression of TIMP-1 and the increase in TIMP expression is also associated with decreased collagenase activity.[18]
Increased expression of TIMP1 has been found to be associated with worse prognosis of various tumors, such aslaryngeal carcinoma[19] ormelanoma.[20]
^Brew K, Dinakarpandian D, Nagase H (March 2000). "Tissue inhibitors of metalloproteinases: evolution, structure and function".Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.1477 (1–2):267–83.doi:10.1016/S0167-4838(99)00279-4.PMID10708863.
^Jourquin J, Tremblay E, Bernard A, Charton G, Chaillan FA, Marchetti E, Roman FS, Soloway PD, Dive V, Yiotakis A, Khrestchatisky M, Rivera S (November 2005). "Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory".The European Journal of Neuroscience.22 (10):2569–78.doi:10.1111/j.1460-9568.2005.04426.x.PMID16307599.S2CID18499513.
Hornebeck W (December 2003). "Down-regulation of tissue inhibitor of matrix metalloprotease-1 (TIMP-1) in aged human skin contributes to matrix degradation and impaired cell growth and survival".Pathologie-Biologie.51 (10):569–73.doi:10.1016/j.patbio.2003.09.003.PMID14622947.
