TIMP1 explained

TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein with a molecular weight of 28 kDa.[1] TIMP1 is expressed from several tissues of organisms.

This protein is a member of the TIMP family. The glycoprotein is a natural inhibitor of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function.

Function

TIMP1 is an inhibitory molecule that regulates matrix metalloproteinases (MMPs), and disintegrin-metalloproteinases (ADAMs and ADAMTSs).[2] In regulating MMPs, TIMP1 plays a crucial role in extracellular matrix (ECM) composition, wound healing,[3] and pregnancy.[4] [5] [6]

The dysregulated activity of TIMP1 has been implicated in cancer.[7] In pregnancy, TIMP1 plays a regulatory role in the process of implantation, particularly the cytotrophoblast invasion of the uterine endometrium.[8] Additionally, it plays a role in regulating the transcriptional profile of fetal and placental tissues associated with the early stages of pregnancy.[9] 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 manipulated in vitro using techniques, like the TIMP1 knock-out.[10] [11] [12]

Other names

Regulation of TIMP expression

Transcription of this gene is highly inducible in response to many cytokines and hormones. In addition, the expression from some but not all inactive X chromosomes suggests that this gene inactivation is polymorphic in human females. This gene is located within intron 6 of the synapsin I gene and is transcribed in the opposite direction.[13]

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.[14]

Increased expression of TIMP1 has been found to be associated with worse prognosis of various tumors, such as laryngeal carcinoma[15] or melanoma.[16]

See also

Further reading

External links

Notes and References

  1. Nee. Larine E.. Mcmorrow. Tara. Campbell. Eric. Slattery. Craig. Ryan. Michael P.. 2004-10-01. TNF-α and IL-1β–mediated regulation of MMP-9 and TIMP-1 in renal proximal tubular cells. Kidney International. 66. 4. 1376–1386. 10.1111/j.1523-1755.2004.00900.x. 15458430 . 0085-2538. free.
  2. Brew K, Nagase H . The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1803 . 1 . 55–71 . January 2010 . 20080133 . 2853873 . 10.1016/j.bbamcr.2010.01.003 .
  3. Brew K, Dinakarpandian D, Nagase H . Tissue inhibitors of metalloproteinases: evolution, structure and function . Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology . 1477 . 1–2 . 267–83 . March 2000 . 10708863 . 10.1016/S0167-4838(99)00279-4 .
  4. Graham CH, Lala PK . Mechanism of control of trophoblast invasion in situ . Journal of Cellular Physiology . 148 . 2 . 228–34 . August 1991 . 1652588 . 10.1002/jcp.1041480207 . 3145982 .
  5. Nothnick WB, Soloway P, Curry TE . Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene . Biology of Reproduction . 56 . 5 . 1181–8 . May 1997 . 9160717 . 10.1095/biolreprod56.5.1181 . free .
  6. Nothnick WB . Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice . Biology of Reproduction . 63 . 3 . 905–12 . September 2000 . 10952938 . 10.1095/biolreprod63.3.905 . free .
  7. Kim YS, Kim SH, Kang JG, Ko JH . Expression level and glycan dynamics determine the net effects of TIMP-1 on cancer progression . BMB Reports . 45 . 11 . 623–8 . 2012 . 23187000 . 4133808 . 10.5483/BMBRep.2012.45.11.233.
  8. Graham CH, Lala PK . Mechanism of control of trophoblast invasion in situ . Journal of Cellular Physiology . 148 . 2 . 228–34 . August 1991 . 1652588 . 10.1002/jcp.1041480207 . 3145982 .
  9. Vincent ZL, Mitchell MD, Ponnampalam AP . Regulation of TIMP-1 in Human Placenta and Fetal Membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine . Reproductive Biology and Endocrinology . 13 . 136 . December 2015 . 26691525 . 4687108 . 10.1186/s12958-015-0132-y . free .
  10. Gong Y, Scott E, Lu R, Xu Y, Oh WK, Yu Q . TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression . PLOS ONE . 8 . 10 . e77366 . 2013-10-15 . 24143225 . 3797040 . 10.1371/journal.pone.0077366 . 2013PLoSO...877366G . free .
  11. Jourquin J, Tremblay E, Bernard A, Charton G, Chaillan FA, Marchetti E, Roman FS, Soloway PD, Dive V, Yiotakis A, Khrestchatisky M, Rivera S . 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 . November 2005 . 16307599 . 10.1111/j.1460-9568.2005.04426.x . 18499513 .
  12. Graham CH, Lala PK . Mechanism of control of trophoblast invasion in situ . Journal of Cellular Physiology . 148 . 2 . 228–34 . August 1991 . 1652588 . 10.1002/jcp.1041480207 . 3145982 .
  13. Web site: Entrez Gene: TIMP1 TIMP metallopeptidase inhibitor 1.
  14. Reichenstein M, Reich R, LeHoux JG, Hanukoglu I . ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells . Molecular and Cellular Endocrinology . 215 . 1–2 . 109–14 . February 2004 . 15026182 . 10.1016/j.mce.2003.11.011 . 10.1.1.538.7614 . 6836003 .
  15. Ma J, Wang J, Fan W, Pu X, Zhang D, Fan C, Xiong L, Zhu H, Xu N, Chen R, Liu S . Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma . International Journal of Clinical and Experimental Pathology . 7 . 1 . 246–54 . Dec 2013 . 24427345 . 3885479 .
  16. Tarhini AA, Lin Y, Yeku O, LaFramboise WA, Ashraf M, Sander C, Lee S, Kirkwood JM . A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma . Journal of Translational Medicine . 12 . 19 . January 2014 . 24457057 . 3909384 . 10.1186/1479-5876-12-19 . free .

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