Top

Published in:

01-07-2010 | Original Article

Relationships between MMP-2, MMP-9, TIMP-1 and TIMP-2 levels and their pathogenesis in patients with lupus nephritis

Authors: Zhongxin Jiang, Tao Sui, Bin Wang

Published in: Rheumatology International | Issue 9/2010

Abstract

Recent evidence suggests that matrix metalloproteinases (MMPs) were involved with many kinds of kidney diseases. We investigated the roles of MMPs and its tissue inhibitors TIMPs in patients with lupus nephritis (LN). A total of 44 systemic lupus erythematosus patients and 31 healthy subjects were enrolled. The levels of total MMP-2, 9 (tMMP-2, tMMP-9) along with TIMP-1, 2 were measured in serum by ELISA. Serum tMMP-2, tMMP-9 was higher in LN patients than those non-LN patients and healthy controls. Serum tMMP-2 in patients without LN was higher than in healthy controls. TIMP-2 was higher in LN patients than healthy controls, and no significant difference in TIMP-2 was observed between LN and non-LN patients. TIMP-1 levels among LN, non-LN patients and healthy controls were comparable. The ratio of tMMP-9 to TIMP-1 in LN patients was higher than non-LN patients and healthy controls and no difference in ratio of tMMP-9 to TIMP-1 between non-LN patients and healthy subjects was observed. A negative correlation between the ratio of tMMP-9 to TIMP-1 in lupus patients and the titers of anti-dsDNA was found; whereas, no correlation between the ratio of tMMP-9 to TIMP-1 and the concentration of C3 as well 24 h urine protein was observed in LN patients. We suggest imbalance between tMMP-9 and TIMP-1 may contribute to the pathogenesis of LN. Measurement of MMPs and TIMPs may be helpful in the early identification of lupus patients with LN and may help gauge the response to treatment in patients with active LN undergoing treatment.

Mills JA (1994) Systemic lupus erythematosus. N Engl J Med 330:1871–1879. doi:10.1056/NEJM199406303302608 CrossRefPubMed

Kotzin BL (1996) Systemic lupus erythematosus. Cell 85:303–306. doi:10.1016/S0092-8674(00)81108-3 CrossRefPubMed

Kelley VR, Wuthrich RP (1999) Cytokines in the pathogenesis of systemic lupus erythematosus. Semin Nephrol 19:57–66PubMed

Perez de Lema G, Maier H, Nieto E, Vielhauer V, Luckow B, Mampaso F, Schlondorff D (2001) Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis. J Am Soc Nephrol 12:1369–1382PubMed

Chang HR, Yang SF, Li ML, Lin CC, Hsieh YS, Lian JD (2006) Relationships between circulating matrix metalloproteinase-2 and -9 and renal function in patients with chronic kidney disease. Clin Chim Acta 366:243–248. doi:10.1016/j.cca.2005.10.007 CrossRefPubMed

Mannello F, Luchetti F, Falcieri E, Papa S (2005) Multiple roles of matrix metalloproteinases during apoptosis. Apoptosis 10:19–24. doi:10.1007/s10495-005-6058-7 CrossRefPubMed

Mannello F, Tonti GA, Bagnara GP, Papa S (2006) Role and function of matrix metalloproteinases in the differentiation and biological characterization of mesenchymal stem cells. Stem Cells 24:475–481. doi:10.1634/stemcells.2005-0333 CrossRefPubMed

Brew K, Dinakarpandian D, Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267–283PubMed

Lambert E, Dasse E, Haye B, Petitfrere E (2004) TIMPs as multifacial proteins. Crit Rev Oncol Hematol 49:187–198. doi:10.1016/j.critrevonc.2003.09.008 CrossRefPubMed

10.

Chang YH, Lin IL, Tsay GJ, Yang SC, Yang TP, Ho KT, Hsu TC, Shiau MY (2008) Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Biochem 41:955–959. doi:10.1016/j.clinbiochem.2008.04.012 CrossRefPubMed

11.

Faber-Elmann A, Sthoeger Z, Tcherniack A, Dayan M, Mozes E (2002) Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus. Clin Exp Immunol 127:393–398. doi:10.1046/j.1365-2249.2002.01758.x CrossRefPubMed

12.

Makowski GS, Ramsby ML (2003) Concentrations of circulating matrix metalloproteinase 9 inversely correlate with autoimmune antibodies to double stranded DNA: implications for monitoring disease activity in systemic lupus erythematosus. Mol Pathol 56:244–247. doi:10.1136/mp.56.4.244 CrossRefPubMed

13.

Ainiala H, Hietaharju A, Dastidar P, Loukkola J, Lehtimäki T, Peltola J, Korpela M, Heinonen T, Nikkari ST (2004) Increased serum matrix metalloproteinase 9 levels in systemic lupus erythematosus patients with neuropsychiatric manifestations and brain magnetic resonance imaging abnormalities. Arthritis Rheum 50:858–865. doi:10.1002/art.20045 CrossRefPubMed

14.

Matache C, Stefanescu M, Dragomir C, Tanaseanu S, Onu A, Ofiteru A, Szegli G (2003) Matrix metalloproteinase-9 and its natural inhibitor TIMP-1 expressed or secreted by peripheral blood mononuclear cells from patients with systemic lupus erythematosus. J Autoimmun 20:323–331. doi:10.1016/S0896-8411(03)00037-4 CrossRefPubMed

15.

Munoz-Valle JF, Vazquez-Del Mercado M, Garcia-Iglesias T, Orozco-Barocio G, Bernard-Medina G, Martínez-Bonilla G, Bastidas-Ramírez BE, Navarro AD, Bueno M, Martínez-López E, Best-Aguilera CR, Kamachi M, Armendáriz-Borunda J (2003) T(H)1/T(H)2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients. Clin Exp Immunol 131:377–384. doi:10.1046/j.1365-2249.2003.02059.x CrossRefPubMed

16.

Mawrin C, Brunn A, Rocken C, Schroder JM (2003) Peripheral neuropathy in systemic lupus erythematosus: pathomorphological features and distribution pattern of matrix metalloproteinases. Acta Neuropathol 105:365–372PubMed

17.

Robak E, Wierzbowska A, Chmiela M, Kulczycka L, Sysa-Jedrejowska A, Robak T (2006) Circulating total and active metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in patients with systemic lupus erythematosus. Mediators Inflamm 2006:17898. doi:10.1155/MI/2006/17898 CrossRefPubMed

18.

Urushihara M, Kagami S, Kuhara T, Tamaki T, Kuroda Y (2002) Glomerular distribution and gelatinolytic activity of matrix metalloproteinases in human glomerulonephritis. Nephrol Dial Transplant 17:1189–1196. doi:10.1093/ndt/17.7.1189 CrossRefPubMed

19.

Tveita AA, Rekvig OP, Zykova SN (2008) Increased glomerular matrix metalloproteinase activity in murine lupus nephritis. Kidney Int 74:1150–1158. doi:10.1038/ki.2008.308 CrossRefPubMed

20.

Barille S, Akhoundi C, Collette M, Mellerin MP, Rapp MJ, Harousseau JL, Bataille R, Amiot M (1997) Metalloproteinases in multiple myeloma: production of matrix metalloproteinase-9 (MMP-9), activation of proMMP-2, and induction of MMP-1 by myeloma cells. Blood 90:1649–1655PubMed

21.

Kelly T, Borset M, Abe E, Gaddy-Kurten D, Sanderson RD (2000) Matrix metalloproteinases in multiple myeloma. Leuk Lymphoma 37:273–281PubMed

22.

Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725. doi:10.1002/art.1780400928 CrossRefPubMed

23.

Liu Y, Zheng M, Yin WH, Zhang B (2004) Relationship of serum levels of HGF and MMP-9 with disease activity of patients with systemic lupus erythematosus. Zhejiang Da Xue Xue Bao Yi Xue Ban 33:340–343, 348

24.

Davies M, Martin J, Thomas GJ, Lovett DH (1992) Proteinases and glomerular matrix turnover. Kidney Int 41:671–678. doi:10.1038/ki.1992.103 CrossRefPubMed

25.

Norman JT, Lewis MP (1996) Matrix metalloproteinases (MMPs) in renal fibrosis. Kidney Int Suppl 54:S61–S63PubMed

26.

Akiyama K, Shikata K, Sugimoto H (1997) Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis. Res Commun Mol Pathol Pharmacol 95:115–118PubMed

27.

Okamoto T (2006) NF-kappaB and rheumatic diseases. Endocr Metab Immune Disord Drug Targets 6:359–372PubMed

28.

Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP (1997) Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74:111–122PubMed

29.

Guedez L, Stetler-Stevenson WG, Wolff L, Wang J, Fukushima P, Mansoor A, Stetler-Stevenson M (1998) In vitro suppression of programmed cell death of B cells by tissue inhibitor of metalloproteinases-1. J Clin Invest 102:2002–2010. doi:10.1172/JCI2881 CrossRefPubMed

30.

Chen TY, Hsieh YS, Yang CC, Wang CP, Yang SF, Cheng YW, Chiou HL (2005) Relationship between matrix metalloproteinase-2 activity and cystatin C levels in patients with hepatic disease. Clin Biochem 38:632–638. doi:10.1016/j.clinbiochem.2005.03.005 CrossRefPubMed

31.

Kuo WH, Chou FP, Lu SC, Chu SC, Hsieh YS (2000) Significant differences in serum activities of matrix metalloproteinase-2 and-9 between HCV and HBV-infected patients and carriers. Clin Chim Acta 294:157–168. doi:10.1016/S0009-8981(00)00182-0 CrossRefPubMed

32.

Yang SF, Chu SC, Chiang IC, Kuo WF, Chiou HL, Chou FP, Kuo WH, Hsieh YS (2005) Excessive matrix metalloproteinase-9 in the plasma of community-acquired pneumonia. Clin Chim Acta 352:209–215. doi:10.1016/j.cccn.2004.09.025 CrossRefPubMed

33.

Rodrigo E, Lopez-Hoyos M, Escallada R, Fernández-Fresnedo G, Ruiz JC, Piñera C, Cotorruelo JG, Zubimendi JA, de Francisco AL, Arias M (2000) Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy. Nephrol Dial Transplant 15:2041–2045. doi:10.1093/ndt/15.12.2041 CrossRefPubMed

34.

Chou FP, Chu SC, Cheng MC, Yang SF, Cheung WN, Chiou HL, Hsieh YS (2002) Effect of hemodialysis on the plasma level of type IV collagenases and their inhibitors. Clin Biochem 35:383–388. doi:10.1016/S0009-9120(02)00331-4 CrossRefPubMed

Title: Relationships between MMP-2, MMP-9, TIMP-1 and TIMP-2 levels and their pathogenesis in patients with lupus nephritis
Authors: Zhongxin Jiang
Tao Sui
Bin Wang
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Rheumatology International / Issue 9/2010
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-009-1135-9

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2010

Effects of (−)-epigallocatechin-3-gallate on cyclooxygenase 2, PGE2, and IL-8 expression induced by IL-1β in human synovial fibroblasts

What is the relationship between disease activity, severity and damage in a large Canadian systemic sclerosis cohort? Results from the Canadian Scleroderma Research Group (CSRG)

A case of primary Sjögren’s syndrome with pulmonary-limited Wegener’s granulomatosis

Polyarthritis with chondronecrosis associated with osteonecrosis, panniculitis and pancreatitis

Lack of association of TLR4 gene Asp299Gly and Thr399Ile polymorphisms with rheumatoid arthritis in Chinese Han population of Yunnan Province

Peripheral ulcerative keratitis: a serious complication of rheumatoid arthritis

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials