title: Cytokine functions of TIMP-1.
abstract: The tissue inhibitors of metalloproteinases (TIMPs) are well recognized for their role in extracellular matrix remodeling by controlling the activity of matrix metalloproteinases (MMPs). Independent of MMP inhibition, TIMPs act as signaling molecules with cytokine-like activities thereby influencing various biological processes including cell growth, apoptosis, differentiation, angiogenesis, and oncogenesis. Recent studies on TIMP-1's cytokine functions have identified complex regulatory networks involving a specific surface receptor and subsequent signaling pathways including miRNA-mediated posttranscriptional regulation of gene expression that ultimately control the fate and behavior of the cells. The present review summarizes the current knowledge on TIMP-1 as a cytokine modulator of cell functions, outlines recent progress in defining molecular pathways that transmit TIMP-1 signals from the cell periphery into the nucleus, and discusses TIMP-1's role as a cytokine in the pathophysiology of cancer and other human diseases.
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University of Munich, Pettenkoferstrasse 9b, 80336, Munich, Germany, christian.ries@med.uni-muenchen.de.
authors: Christian
authors: C
authors: Ries
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D019715:Tissue Inhibitor of Metalloproteinase-1
references: J Neurobiol. 2006 Jan;66(1):82-94
references: 16216006
references: J Surg Res. 2002 Jan;102(1):39-44
references: 11792150
references: Mol Aspects Med. 2008 Oct;29(5):258-89
references: 18762209
references: Blood. 1998 Aug 15;92(4):1342-9
references: 9694723
references: Dev Genes Evol. 2003 Aug;213(8):382-9
references: 12736828
references: J Cell Sci. 1994 Sep;107 ( Pt 9):2373-9
references: 7844157
references: Prog Clin Biol Res. 1985;184:95-104
references: 3931094
references: Science. 1995 Feb 10;267(5199):891-3
references: 7531366
references: Infect Immun. 2004 Jan;72(1):82-8
references: 14688084
references: J Cell Biol. 1996 Dec;135(6 Pt 1):1669-77
references: 8978831
references: Cell. 2006 Nov 3;127(3):469-80
references: 17081971
references: Dev Biol. 1999 Jul 15;211(2):238-54
references: 10395785
references: Breast Cancer Res Treat. 2009 Sep;117(1):31-44
references: 18787947
references: Cancer Metastasis Rev. 2009 Jun;28(1-2):35-49
references: 19169797
references: Leukemia. 2007 Apr;21(4):595-603
references: 17301822
references: J Biol Chem. 1989 Oct 15;264(29):17374-8
references: 2793861
references: J Mol Cell Cardiol. 2010 Mar;48(3):445-53
references: 19799912
references: Cancer Immunol Immunother. 2009 Mar;58(3):361-71
references: 18618109
references: J Neurosci. 2005 May 18;25(20):4917-29
references: 15901773
references: Radiat Res. 2004 Feb;161(2):174-84
references: 14731072
references: Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3509-13
references: 8622967
references: PLoS One. 2012;7(9):e44081
references: 22957045
references: Int J Cancer. 1998 Jan 19;75(2):246-53
references: 9462715
references: J Clin Invest. 1998 Dec 1;102(11):2002-10
references: 9835626
references: Nature. 1985 Nov 7-13;318(6041):66-9
references: 3903517
references: Exp Cell Res. 2004 Dec 10;301(2):158-67
references: 15530852
references: Blood. 2005 Feb 15;105(4):1660-8
references: 15479729
references: Genome Biol. 2011 Nov 11;12(11):233
references: 22078297
references: Cell. 2010 Apr 2;141(1):52-67
references: 20371345
references: J Biol Chem. 2010 Feb 26;285(9):6508-14
references: 20056610
references: Exp Hematol. 2013 Sep;41(9):823-831.e2
references: 23660069
references: Biochem Biophys Res Commun. 1990 Sep 28;171(3):1264-71
references: 1699524
references: J Biol Chem. 1999 Jul 23;274(30):21362-8
references: 10409697
references: J Invest Dermatol. 1991 Oct;97(4):679-85
references: 1940438
references: Cell Death Dis. 2012 Jun 28;3:e332
references: 22739984
references: Cancer. 2005 Apr 15;103(8):1676-84
references: 15754326
references: Crit Rev Oncol Hematol. 2004 Mar;49(3):187-98
references: 15036259
references: Leuk Res. 2010 Mar;34(3):399-402
references: 19781774
references: Nat Med. 2003 Apr;9(4):407-15
references: 12652295
references: Clin Cancer Res. 2011 Apr 15;17(8):2417-25
references: 21487066
references: J Gastrointestin Liver Dis. 2011 Sep;20(3):287-91
references: 21961097
references: Oncogene. 2006 May 18;25(21):3041-8
references: 16407831
references: Nature. 1985 Jun 27-Jul 3;315(6022):768-71
references: 3839290
references: Int J Cancer. 2010 Jan 15;126(2):362-70
references: 19609944
references: FEBS Lett. 1992 Jan 20;296(2):231-4
references: 1370805
references: Am J Cardiol. 2010 Aug 15;106(4):477-82
references: 20691304
references: FEBS Lett. 2013 May 21;587(10):1524-8
references: 23583449
references: Ann N Y Acad Sci. 1999 Jun 30;878:522-3
references: 10415761
references: Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):E309-16
references: 22223664
references: J Cell Biol. 1994 Feb;124(4):619-26
references: 8106557
references: Hepatology. 2008 Aug;48(2):688-9; author reply 689-90
references: 18666227
references: Int J Cancer. 2005 Jul 20;115(6):849-60
references: 15729716
references: J Cell Biochem. 2008 Aug 1;104(5):1803-17
references: 18384129
references: J Natl Cancer Inst. 1995 Feb 15;87(4):293-8
references: 7535861
references: Mol Cell. 2004 Feb 13;13(3):329-40
references: 14967141
references: J Neurosci Res. 2009 Jul;87(9):2115-25
references: 19235898
references: Nat Rev Mol Cell Biol. 2007 Mar;8(3):221-33
references: 17318226
references: Ann Clin Lab Sci. 2006 Winter;36(1):23-30
references: 16501233
references: J Cell Physiol. 2010 Jan;222(1):219-29
references: 19780057
references: Blood. 2011 Jun 16;117(24):6479-88
references: 21521782
references: Int J Biochem Cell Biol. 2009 May;41(5):1102-15
references: 19010442
references: Obesity (Silver Spring). 2010 Mar;18(3):638-40
references: 19730423
references: Clin Exp Metastasis. 2011 Feb;28(2):91-9
references: 21053058
references: Biomarkers. 2008 Aug;13(5):549-56
references: 18979644
references: Biol Chem. 2004 Jul;385(7):655-63
references: 15318815
references: Cancer Res. 2007 Sep 15;67(18):8615-23
references: 17875701
references: J Biol Chem. 2003 Oct 10;278(41):40364-72
references: 12904305
references: Clin Exp Metastasis. 2011 Dec;28(8):793-802
references: 21789719
references: EMBO J. 2006 Sep 6;25(17):3934-42
references: 16917503
references: Blood. 1995 Dec 15;86(12):4506-15
references: 8541540
references: Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1590-5
references: 17545477
references: Blood. 1997 Mar 1;89(5):1708-15
references: 9057654
references: Science. 1999 Apr 2;284(5411):143-7
references: 10102814
references: Biochem J. 2003 Jun 15;372(Pt 3):767-74
references: 12639219
references: Biochem Biophys Res Commun. 2004 Nov 5;324(1):440-5
references: 15465038
references: Blood. 2001 Mar 15;97(6):1796-802
references: 11238122
references: Mol Cells. 2011 Mar;31(3):225-30
references: 21350939
references: J Clin Invest. 1998 Mar 15;101(6):1478-87
references: 9502791
references: Cell. 2009 Jan 23;136(2):215-33
references: 19167326
references: J Biol Chem. 2002 Mar 29;277(13):11069-76
references: 11796725
references: Calcif Tissue Int. 2006 May;78(5):285-92
references: 16691494
references: Exp Hematol. 1993 Jan;21(1):169-76
references: 8417953
references: FEBS Lett. 1992 Feb 17;298(1):29-32
references: 1544418
references: J Clin Invest. 2002 Oct;110(8):1105-11
references: 12393846
references: Acta Oncol. 2008;47(4):580-90
references: 18465326
references: Biochem Biophys Res Commun. 1975 Sep 16;66(2):747-54
references: 170930
references: Cancer Res. 2005 Feb 1;65(3):898-906
references: 15705888
references: J Biol Chem. 1996 Nov 29;271(48):30375-80
references: 8939999
references: Cancer Metastasis Rev. 2008 Mar;27(1):57-66
references: 18058195
references: PLoS One. 2012;7(6):e38773
references: 22701711
references: Sci Signal. 2008 Jul 08;1(27):re6
references: 18612141
references: Cancer. 2011 Feb 1;117(3):517-25
references: 20862742
references: Biochemistry. 1991 Aug 20;30(33):8097-102
references: 1868085
references: Nat Rev Cancer. 2002 Mar;2(3):161-74
references: 11990853
references: Curr Eye Res. 1998 Jan;17(1):47-52
references: 9472470
references: J Biol Chem. 2001 May 4;276(18):15498-503
references: 11279011
references: J Hypertens. 2012 Jan;30(1):3-16
references: 22134384
references: Biochem Biophys Res Commun. 2002 Aug 9;296(1):201-5
references: 12147251
references: Biochem Biophys Res Commun. 2011 Apr 8;407(2):277-82
references: 21300026
references: Genes Dev. 1999 Jan 1;13(1):35-48
references: 9887098
references: Biol Chem. 2012 Dec;393(12):1463-70
references: 23667903
references: Nature. 1997 Apr 17;386(6626):671-4
references: 9109485
references: Trends Mol Med. 2005 Mar;11(3):97-103
references: 15760767
references: J Neurochem. 2006 Jul;98(1):234-47
references: 16805810
references: J Biol Chem. 1984 Aug 25;259(16):9992-6
references: 6332112
references: PLoS One. 2009 Dec 14;4(12):e8289
references: 20011518
references: J Neurooncol. 2009 Oct;95(1):117-128
references: 19430729
references: Exp Cell Res. 2009 May 15;315(9):1584-92
references: 18930046
references: Hum Pathol. 2012 Aug;43(8):1184-91
references: 22397869
references: Biomarkers. 2011 Jul;16 Suppl 1:S31-41
references: 21707442
references: PLoS One. 2010 Sep 30;5(9):
references: 20941363
references: J Biol Chem. 1999 Oct 22;274(43):31108-13
references: 10521512
references: Biochim Biophys Acta. 2010 Jan;1803(1):55-71
references: 20080133
references: Blood. 2007 May 1;109(9):4055-63
references: 17197427
references: Mol Aspects Med. 2008 Oct;29(5):290-308
references: 18619669
references: Oncogene. 2006 Mar 9;25(10):1496-508
references: 16261161
references: Cell Transplant. 2012;21(9):1931-44
references: 22449760
references: Cell. 2003 Jul 25;114(2):171-80
references: 12887919
references: J Biol Chem. 1992 Aug 25;267(24):17321-6
references: 1512267
references: Cancer Lett. 2008 Sep 28;269(1):37-45
references: 18502033
references: Leuk Res. 2010 May;34(5):576-7
references: 19878997
references: Biol Chem. 2009 Sep;390(9):893-7
references: 19558322
references: Stem Cells. 2006 Aug;24(8):1892-903
references: 16690780
references: Oncogene. 2003 Apr 10;22(14):2121-34
references: 12687014
references: Biochem Biophys Res Commun. 1975 May 5;64(1):232-40
references: 167734
references: FEBS Lett. 2000 Nov 24;485(2-3):117-21
references: 11094152
references: Cancer Res. 1999 Dec 15;59(24):6267-75
references: 10626822
references: Diabetes. 2001 May;50(5):1047-55
references: 11334407