Tissue Inhibitor of Metalloproteinases 1 (TIMP-1)
Tissue Inhibitor of Metalloproteinases 1 (TIMP-1) is a member of a family of secreted proteolytic enzymes that are involved in the biosynthesis of connective tissue. The synthesis and secretion of matrix metalloproteinases (MMPs) is induced in various cell types by a number of cytokines. Metalloproteinases degrade constituents of the basal membrane and the extracellular matrix, including collagens, proteoglycans, gelatin, fibronectin, laminin, and elastin, under physiological and pathological conditions. The biological activities of the proteases are subject to a complex regulation also involving specific inhibitors, called TIMP (Tissue inhibitor of metalloproteinases). Many proforms of these metalloproteinases form complexes with these inhibitors. TIMP-1 is a major regulator of extracellular matrix synthesis and degradation. A certain balance of MMPs and TIMPs is essential for tumor growth and health. It complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. TIMP-1 also mediates erythropoiesis in vitro but, unlike IL-3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. It is known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-16 though it does not act on MMP-14.
Swiss-Prot Accession Number: P01033
PublicationsA matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis (2021) Alexander Jr LC, McHorse G, Huebner JL, Bay-Jensen AC, Karsdal MA, Kraus VB Arthritis Research & Therapy
Distinct patterns of blood cytokines beyond a cytokine storm predict mortality in COVID-19 (2021) Herr C, Mang S, Mozafari B, Guenther K, Speer T, seibert M, Srikakulam SK, Beisswenger C, Ritzmann F, Keller A, Mueller R, smola S, Eisinger D, Zemlin M, Danziger G, Volk T, Hoersch S, Krawczyk M, Lammert F, Adams T, Wagenpfeil G, Kindermann M, Marcu C, Ataya ZWD, Mittag M, Schwarzkopf K, Custodis F, Grandt D, Schaefer H, Eltges K, Lepper PM, Bals R Journal of Inflammation Research
Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers (2020) Schubauer-Berigan MK, Dahm MM, Toennis CA, Sammons DL, Eye T, Kodali V, Zeidler-Erdely PC, Erdely A Nanotoxicology
Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-ßRI inhibitor galunisertib. (2020) Giannelli G, Santoro A, Kelley RK, Gane E, Paradis V, Cleverly A, Smith C, Estrem ST, Man M, Wang S, Lahn MM, Raymond E, Benhadji KA, Faivre S PLoS One
Serum biomarkers that predict lean mass loss over bed rest in older adults: An exploratory study (2020) Gawel SH, Davis GJ, Luo M, Deutz NEP, Wolfe RR, Pereira SL Clinica Chimica Acta
Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitnes in old age (2020) Brigger D, Riether C, van Brummelen R, Mosher KI, Shiu A, Ding Z, Zbaren N, Gasser P, Guntern P, Yousef H, Castellano JM, Storni F, Graff-Radford N, Britschgi M, Grandgirard D, Hinterbrandner M, Siegrist M, Moullan N, Hofstetter W, Leib SL, Villiger PM, Auwerx J, Villeda SA, Wyss-Coray T, Noti M, Eggel A Nature Metabolism
Metabolomic analyses reveal lipid abnormalities and hepatic dysfunction in non-human primate model for Yersinia pestis (2019) Gautam A, Muhie S, Cakraborty N, Hoke A, Donohue D, Miller SA, Hammamieh R, Jett M Metabolomics
External Validation of a Pre-Transplant Biomarker Model (REVERSE) Predictive of Renal Recovery after Liver Transplantation (2019) Levitsky J, Asrani SK, Abecassis M, Ruiz R, Jennings LW, Klintmalm G Hepatology
Biomarkers of Community-Acquired Pneumonia: A Key to Disease Diagnosis and Management (2019) Savvateeva EN, Rubina AY, Gryadunov DA BioMed Research International
Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation. (2019) Haraden CA, Huebner JL, Hsueh MF, Li YJ, Kraus VB Arthritis Research & Therapy
Biomarker panels associated with progression of renal disease in type 1 diabetes. (2019) Colombo M, Valo E, McGurnaghan SJ, Sandholm N, Blackbourn LAK, Dalton RN, Dunger D, Groop PH, McKeigue PM, Forsblom C, Colhoun HM Diabetologia
Hypothesis: cerebrospinal fluid protein markers suggest a pathway toward symptomatic resilience to AD pathology (2019) Meyer PF, Savard M, Poirier J, Morgan D, Breitner J, for the Alzheimer's Disease Neuroimaging Initiative Alzheimer's & Dementia
Major depression and enhanced molecular senescence abnormalities in young and middle-aged adults. (2019) Diniz BS, Reynolds Iii CF, Sibille E, Bot M, Penninx BWJH Translational Psychiatry
Discovery and validation of a biomarker model (preserve) predictive of renal outcomes after liver transplantation (2019) Levitsky J, Asrani SK, Klintmalm G, Schiano T, Moss A, Chavin K, Miller C, Guo K, Zhao L, Jennings LW, Brown M, Armstrong B, Abecassis M Hepatology
A Machine-Learning Approach to Identify a Prognostic Cytokine Signature That Is Associated With Nivolumab Clearance in Patients With Advanced Melanoma. (2019) Wang R, Shao X, Zheng J, Saci A, Qian X, Pak I, Roy A, Bello A, Rizzo JI, Hosein F, Moss RA, Wind-Rotolo M, Feng Y Clinical Pharmacology and Therapeutics
Development of a prognostic composite cytokine signature based on the correlation with nivolumab clearance: translational PK/PD analysis in patients with renal cell carcinoma. (2019) Wang R, Zheng J, Shao X, Ishii Y, Roy A, Bello A, Lee R, Zhang J, Wind-Rotolo M, Feny Y Journal for ImmunoTherapy of Cancer
Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection (2019) Malachowa N, Kobayashi SD, Porter AR, Freedman B, Hanley PW, Lovaglio J, Saturday GA, Gardner DJ, Scott DP, Griffin A, Cordova K, Long D, Rosenke R, Sturdevant DE, Bruno D, Martens C, Kreiswirth BN, DeLeo FR mBio
Von Willebrand factor and ADAMTS13 activity in relation to risk of dementia: a population-based study (2018) Wolters F, Boender J, de Vries P, Sonneveld M, Koudstaal P, de Maat M, Franco O, Ikram M, Leebeek F, Ikram MA Scientific Reports 2018 Apr
Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment (2018) van den Ham HJ, Cooper J, Tomasik J, Bahn S, Aerts J, Oseterhaus A, Gruters R, Andeweg A PLoS One
Key Proteins Involed in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity (2018) Dittrich A, Grimm D, Sahana J, Bauer J, Kruger M, Infanger M, Magnusson N Cellular Physiology and Biochemistry 2018
Carbon nanotube and nanofiber exposure and sputum and blood biomarkers of early effect among U.S. workers (2018) Beard JD, Erdely A, Dahm MM, de Perio MA, Birch ME, Evans DE, Fernback JE, Eye T, Kodali V, Mercer RR, Bertke SJ, Schubauer-Berigan MK Environmental Internation 116 (2018)
Synergistic Cytokine Effects as Apremilast Response Predictors in Patients With Psoriasis (2018) Garcet S, Nograles K, Correa da Rosa J, Schafer PH, Krueger JG Journal of Allergy and Clinical Immunology
Testing a multivariate proteomic panel for TBI biomarker discovery: A track-TBI pilot study (2018) Huie JR, Diaz-Arrastia R, Yue JK, Sorani M, Puccio A, Okonkwo DO, Manley GT, Ferguson AR Journal of Neurotrauma
Early Plasma Matrix Metalloproteinase Profiles: A Novel Pathway in Pediatric Acute Respiratory Distress Syndrom (2018) Zinter MS, Delucchi KL, Kong MY, Orwoll BE, Spicer AS, Lim MJ, Alkhouli MF, Ratiu AE, McKenzie AV, McQuillen PS, Dvorak CC, Calfee CS, Matthay MA, Sapru A American Journal of Respiratory and Critical Care Medicine
Elevated circulating MMP-9 is linked to increased COPD exacerbation in SPIROMICS and COPDGene (2018) Wells JM, Parker MM, Oster RA, Bowler RP, Dransfield MT, Bhatt SP, Cho MH, Kim V, Curtis JL, Martinez FJ, Paine R 3rd, O'Neal W, Labaki WW, Kaner RJ, Barjaktarevic I, Han MK, Silverman EK, Crapo JD, Barr RG, Woodruff P, Castaldi PJ, Gaggar A JCI Insight
Serum Apolipoprotein E and Other Inflammatory Markers Can Identify Non-Responding Patients to a Dendritic Cell Vaccine (2018) Leeman H, Kaminska E, Green D, Bodman-Smith M, Gravett A, Bodman-Smith K, Copier J, Coulton G, Fusi A, Dalgleish AG Translational Oncology
Usefulness of Multiple Biomarkers for Predicting Incident Major Adverse Cardiac Events in Patients Undergoing Diagnostic Coronary Angiography (From the Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA] Study) (2017) McCarthy CP, Van Kimmenade R, Gaggin HK, Simon ML, Ibrahim NE, Gandhi P, Kelly N, Motiwala SR, Belcher AM, Harisiades J, Magaret CA, Rhyne RF, Januzzi Jr. JL Am J Cardiol
Serum proteins mediate depression’s association with dementia (2017) Royall DR, Al-Rubaye S, Bishnoi R, Palmer RF Plos One
Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine. (2017) Warnke E, Pietsch J, Kopp S, Bauer J, Sahana J, Wehland M, Krüger M, Hemmersbach R, Infanger M, Lützenberg R, Grimm D Cell Physiol Biochem.
High false-positive rate of a putative biomarker test to aid in the diagnosis of schizophrenia (2016) Wehler CA, Preskorn, SH Journal of Clinical Psychiatry
Effects of Acute Endurance Exercise on Plasma Protein Profiles of Endurance-Trained and Untrained Individuals over Time (2016) Schild M, Eichner G, Beiter T, Zuegel M, Niess AM, Steinacker JM, Mooren FC Mediators of Inflammation
Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria*American Journal of Nephrology (2016) Brooks ER, Hoppe B, Milliner DS, Salido E, Rim J, Krevitt LM, Olson JB, Price HE, Vural G, Langman CB American Journal of Nephrology
Circulating Biomarkers and Outcome from a Randomised Phase Ii Trial of Sunitinib Vs Everolimus for Patients with Metastatic Renal Cell Carcinoma (2016) Voss MH, Chen D, Marker M, Hakimi AA, Lee C-H, Hsieh JJ, Knox JJ, Voi M, Motzer RJ British Journal of Cancer
Variation in Serum Biomarkers with Sex and Female Hormonal Status: Implications for Clinical Tests (2016) Ramsey JM, Cooper JD, Penninx BWJH, Bahn S Scientific Reports
Blood-based immune-endocrine biomarkers of treatment response in depression (2016) Chan MK, Cooper JD, Bot M, Birkenhanger TK, Bergink V, Drexhage HA, Steiner J, Rothermundt M, Penninx BWJH, Bahn S Journal of Psychiatric Research
Serum biomarkers and changes in clinical/MRI evidence of golimumab-treated patients with ankylosing spondylitis: results of the randomized, placebo-controlled GO-RAISE study (2016) Inman RD, Baraliakos X, Hermann KA, Braun J, Deodhar A, Heijde D, Xu S, and Hsu B Arthritis Res Ther.
Characterizing the Inflammatory Response in Esophageal Mucosal Biopsies in Children with Eosinophilic Esophagitis (2016) Sayej WN, Menoret A, Maharjan AS, Fernandez M, Wang Z, Balarezo F, Hyams JS, Sylvester FA, Vella AT Clinical & Translational Immunology
THU0223 Serum Biomarkers Associated with Changes in Asdas and MRI Following Treatment of Ankylosing Spondylitis with Golimumab (2015) Inman RD, Baraliakos X, Hermann KG, Braun J, Deodhar A, van der Heijde DF, Xu S, Hsu B Ann Rheum Dis
Shared Immune and Repair Markers During Experimental Toxoplasma Chronic Brain Infection and Schizophrenia (2015) Tomasik J, Schultz TL, Kluge W, Yolken RH, Bahn S, Carruthers VB Schizophr Bull
Markers of inflammation are associated with clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab (2015) Sznol M, Fishman M, Escudier B, McDermott DF, Kluger H, Stadler WM, Perez-Gracia J, McNeel DG, Curti BD, Harrison MR, Plimack ER, Appleman L, Fong L, Drake CG, Young TC, Chasalow SD, Ross-MacDonald P, Simon JS, Walker D, Choueiri TK J Immunother Cancer
Characterization of Renal Biomarkers for Use in Clinical Trials: Effect of Preanalytical Processing and Qualification Using Samples from Subjects with Diabetes (2015) Brott DA, Furlong ST, Adler SH, Hainer JW, Arani RB, Pinches M, Rossing P, Chaturvedi N Drug Design, Development and Therapy
Implementing lessons learned from previous bronchial biopsy trials in a new randomized controlled COPD biopsy trial with roflumilast (2014) Barnes NC, Saetta M, Rabe KF BMC Pulm Med. 2014 Jan 31;14(1):9
Discovery of Emphysema Relevant Molecular Networks from an A/J Mouse Inhalation Study Using Reverse Engineering and Forward Simulation (REFS™) (2014) Xiang Y, Kogel U, Gebel S, Peck MJ, Peitsch MC, Akmaev VR, Hoeng J Gene Regul Syst Bio. 2014 Feb 19;8:45-61
Plasma protein biomarkers enhance the clinical prediction of kidney injury recovery in patients undergoing liver transplantation. (2014) Levitsky J, Baker TB, Jie C, Ahya S, Levin M, Friedewald J, Al-Saden P, Salomon DR, Abecassis MM. Hepatology 2014 Jul 31. doi: 10.1002/hep.27346. [Epub ahead of print]
An integrated omics analysis: impact of microgravity on host response to lipopolysaccharide in vitro (2014) Chakraborty N, Gautam A, Muhie S, Miller SA, Jett M, Hammamieh R. BMC Genomics 2014 Aug 7;15(1):659. [Epub ahead of print]
Serum protein profiling reveals baseline and pharmacodynamic biomarker signatures associated with clinical outcome in mCRC patients treated with chemotherapy ± cediranib. (2014) Pommier AJ, Shaw R, Spencer SK, Morgan SR, Hoff PM, Robertson JD, Barry ST, Jürgensmeier JM. British Journal of Cancer 2014 Aug 14. doi: 10.1038/bjc.2014.436. [Epub ahead of print]
EFFECTS OF CONTRAST MEDIA ON DIFFERENT URINARY BIOMARKERS OF KIDNEY INJURY (2013) Steffgen J, Blaschke S, Brun-Schulte-Wissing N, Pagel P, Huber F, Mapes J, Jaehnige A, Pestel S Nephrol. Dial. Transplant. (2013) 28 (suppl 1): i331-i351.
A phase II clinical trial of the Vascular Disrupting Agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma (2013) Nowak AK, Brown C, Millward MJ, Creaney J, Byrne MJ, Hughes B, Kremmidiotis G, Bibby DC, Leske AF, Mitchell PL, Pavlakis N, Boyer M, Stockler MR Lung Cancer. 2013 Jun 17. pii: S0169-5002(13)00218-3
Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space (2013) Ma X, Pietsch J, Wehland M, Schulz H, Saar K, Hübner N, Bauer J, Braun M, Schwarzwälder A, Segerer J, Birlem M, Horn A, Hemmersbach R, Waßer K, Grosse J, Infanger M, Grimm D FASEB J. 2013 Nov 6. [Epub ahead of print]
Cytokine Profile Changes In 309 Myelofibrosis Patients: Comparison Of JAK1/JAK2 Inhibitor Therapy Vs. Placebo – Correlative Analysis From The Comfort-I Trial (2013) Dueck AC, Cleeland CS, Dantzer R, Sloan J, Verstovsek S, Emanuel RM, Geyer HL, Mesa RA Blood October 21, 2013 vol. 122 no. 21 4074
Multiplex immunoassay analysis of plasma shows prominent upregulation of growth factor activity pathways linked to GSK3ß signaling in bipolar patients (2013) Haenisch F, Alsaif M, Guest PC, Rahmoune H, Dickerson F, Yolken R, Bahn S Journal of Affective Disorders
Proteins involved in extracellular matrix dynamics are associated with respiratory syncytial virus disease severity (2012) Schuurhof A, Bont L, Hodemaekers HM, de Klerk A, de Groot H, Hofland RW, van de Pol AC, Kimpen JL, Janssen R Eur Respir J. 2012 Jun;39(6):1475-81
Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma (2012) Xu BJ, An QA, Srinivasa Gowda S, Yan W, Pierce LA, Abel TW, Rush SZ, Cooper MK, Ye F, Shyr Y, Weaver KD, Thompson RC Int J Oncol. 2012 Jun;40(6):1995-2003
Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease (2012) Doecke JD, Laws SM, Faux NG, Wilson W, Burnham SC, Lam CP, Mondal A, Bedo J, Bush AI, Brown B, De Ruyck K, Ellis KA, Fowler C, Gupta VB, Head R, Macaulay SL, Pertile K, Rowe CC, Rembach A, Rodrigues M, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Ames D, Masters CL, Martins RN; for the Alzheimer's Disease Neuroimaging Initiative and Australian Imaging Biomarker and Lifestyle Research Group Arch Neurol. 2012 Jul 16:1-8
Screening for New Biomarkers for Subcortical Vascular Dementia and Alzheimer’s Disease (2011) Öhrfelt A, Andreasson U, Simon A, Zetterberg H, Edman A, Potter W, Holder D, Devanarayan V, Seeburger J, Smith AD, Blennow K, Wallin A Dement Geriatr Cogn Disord Extra 1: 31–42.
Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV (2011) Casrouge A, Decalf J, Ahloulay M, Lababidi C, Mansour H, Vallet-Pichard A, Mallet V, Mottez E, Mapes J, Fontanet A, Pol S, Albert ML J Clin Invest. 121: 308-317.
Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase 1/2 study in patients with myelofibrosis (2011) Guglielmelli P, Barosi G, Rambaldi A, Marchioli R, Masciulli A, Tozzi L, Biamonte F, Bartalucci N, Gattoni E, Lupo ML, Finazzi G, Pancrazzi A, Antonioli E, Susini MC, Pieri L, Malevolti E, Usala E, Occhini U, Grossi A, Caglio S, Paratore S, Bosi A, Barbui T, Vannucchi AM Blood. 2011 Jul 1. [Epub ahead of print]
Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study (2010) Visvanathan S, Rahman MU, Keystone E, Genovese M, Klareskog L, Hsia E, Mack M, Buchanan J, Elashoff M, Wagner C Arthritis Res Ther. 12:R211
Bevacizumab therapy normalizes the pathological intraocular environment beyond neutralizing VEGF (2010) Sharma RK, Rogojina AT, Chalam KV Mol Vi. 16: 2175-2184.
Validation of a Blood-Based Laboratory Test to Aid in the Confirmation of a Diagnosis of Schizophrenia (2010) Schwarz E, Izmailov R, Spain M, Barnes A, Mapes JP, Guest PC, Rahmoune H, Pietsch S, Leweke FM, Rothermundt M, Steiner J, Koethe D, Kranaster L, Ohrmann P, Suslow T, Levin Y, Bogerts B, (JM) van Beveren N, McAllister G, Weber N, Niebuhr D, Cowan D, Yolken RH, Bahn S Biomark Insights5: 39–47.
Multi analyte profiling and variability of inflammatory markers in blood and induced sputum in patients with stable COPD (2010) Aaron SD, Vandemheen KL, Ramsay T, Zhang C, Avnur Z, Nikolcheva T, Quinn A Respir Res. 2010 Apr 22;11:41
Peripheral Blood Biomarkers Predict Disease Progression And Mortality In IPF (2010) Richards TJ, Lindell KO, Klesen M, Kaminski N, Zhang Y, Gibson KF Am J Respir Crit Care Me 181: A1120.
Dysregulated macrophage-inflammatory protein-2 expression drives illness in bacterial superinfection of influenza. (2010) Zavitz CC, Bauer CM, Gaschler GJ, Fraser KM, Strieter RM, Hogaboam CM, Stampfli MR J Immunol 184: 2001-2013.
Matrix metalloproteinases during and outside of migraine attacks without aura. (2009) Ashina M, Tvedskov JF, Lipka K, Bilello J, Penkowa M, Olesen J Cephalalgia 30: 303-310.
Regression of Human Pancreatic Tumor Xenografts in Mice After a Single Systemic Injection of Recombinant Vaccinia Virus GLV-1h68. (2009) Yu YA, Galanis C, Woo Y, Chen N, Zhang Q, Fong Y, Szalay AA Mol Cancer Ther 8: 141-151.
Multianalyte profiling of serum antigens and autoimmune and infectious disease molecules to identify biomarkers dysregulated in epithelial ovarian cancer. (2008) Bertenshaw GP, Yip P, Seshaiah P, Zhao J, Chen TH, Wiggins WS, Mapes JP, Mansfield BC Cancer Epidemiol Biomarkers Prev 17: 2872-81.
Biomarker analysis by fluorokine multianalyte profiling distinguishes patients requiring intervention from patients with long-term quiescent coronary artery disease: a potential approach to identify atherosclerotic disease progression. (2008) Gurbel PA, Kreutz RP, Bliden KP, DiChiara J, Tantry US Am Heart J 155: 56-61.
The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. (2007) Kharitonenkov A, Wroblewski VJ, Koester A, Chen YF, Clutinger CK, Tigno XT, Hansen BC, Shanafelt AB, Etgen GJ Endocrinology 148: 774-81.