Effects of Tumor Necrosis Factor Alpha on the Expression of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in Keratoconus Fibroblasts_Journal of Biomedical Engineering

Authors：

FENGPengfei ¹ , LIXiaona ¹ ,  CHENWeiyi ¹ , HERui ² , WANGXiaojun ¹

1. Institute of Applied Mechanics and Biomedical Engineering, Shanxi Key Lab. of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China;
2. Excimer Laser Department, Shanxi Eye Hospital, Taiyuan 030023, China;

Corresponding author：

CHENWeiyi, Email: chenweiyi211@163.com

Keywords：

tumor necrosis factor; keratoconus; corneal fibroblasts; matrix metalloproteinase; tissue inhibitors of matrix metalloproteinase

DOI：

10.7507/1001-5515.20160181

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

The aim of this article is to study the effect of tumor necrosis factor alpha (TNF-α) on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in keratoconus fibroblasts in vitro. Normal cornea and keratoconus fibroblasts were extracted using enzyme digestion method and were cultured in the medium containing TNF-α (0, 10 and 100 ng/mL). The expression of MMPs proteins in the supernatant of corneal fibroblasts and the expression of TIMPs in the normal cornea and keratoconus fibroblasts were detected by Western blot and real-time quantitative polymerase chain reaction respectively. The active form of MMP1 could be detected in the supernatant of keratoconus fibroblasts and upregulated by TNF-α. TNF-α could increase the protein expression of MMP2, MMP3, MMP9 in the supernatant of keratoconus fibroblasts and decrease the gene expression of TIMP1, TIMP2 in keratoconus fibroblasts. The increased MMPs and the decreased TIMPs can increase the degradation of the extracellular matrix. TNF-α may play an important role in the occurrence and development of keratoconus by regulating the expression of MMPs/TIMPs.

Citation： FENGPengfei, LIXiaona, CHENWeiyi, HERui, WANGXiaojun. Effects of Tumor Necrosis Factor Alpha on the Expression of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in Keratoconus Fibroblasts. Journal of Biomedical Engineering, 2016, 33(6): 1139-1144. doi: 10.7507/1001-5515.20160181 Copy

1.	CHOPRA I, JAIN A K. Between eye asymmetry in keratoconus in an Indian population[J]. Clinical and Experimental Optometry, 2005, 88(3): 146-152.
2.	ZADNIK K, STEGER M K, FINK B A, et al. Between-eye asymmetry in keratoconus[J]. Cornea, 2002, 21(7): 671-679.
3.	WEED K H, MCGHEE C N, MACEWEN C J. Atypical unilateral superior keratoconus in young males[J]. Cont Lens Anterior Eye, 2005, 28(4): 177-179.
4.	NIELSEN K, HJORTDAL J, PIHLMANN M, et al. Update on the keratoconus genetics[J]. Acta Ophthalmol (Copenh), 2013, 91(2): 106-113.
5.	RABINOWITZ Y S. Keratoconus[J]. Surv Ophthalmol, 1998, 42(4): 297-319.
6.	LEMA I, SOBRINO T, DURÁN J A, et al. Subclinical keratoconus and inflammatory molecules from tears[J]. Br J Ophthalmol, 2009, 93(6): 820-824.
7.	POULIQUEN Y, BUREAU J, MIRSHAHI M, et al. Keratoconus and inflammatory processes[J]. Bulletin de la Société belge d'ophtalmologie, 1996, 262: 25-28.
8.	YOON K C, JEONG I Y, PARK Y G, et al. Interleukin-6 and tumor necrosis factor-alpha levels in tears of patients with dry eye syndrome[J]. Cornea, 2007, 26(4): 431-437.
9.	PRADA J, NOELLE B, BAATZ H, et al. Tumour necrosis factor alpha and interleukin 6 gene expression in keratocytes from patients with rheumatoid corneal ulcerations[J]. Br J Ophthalmol, 2003, 87(5): 548-550.
10.	PANNEBAKER C, CHANDLER H L, NICHOLS J J. Tear proteomics in keratoconus[J]. Mol Vis, 2010, 16: 1949-1957.
11.	BALASUBRAMANIAN S A, MOHAN S, PYE D C, et al. Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus[J]. Acta Ophthalmol (Copenh), 2012, 90(4): E303-E309.
12.	LEMA I, DURÁN J A. Inflammatory molecules in the tears of patients with keratoconus[J]. Ophthalmology, 2005, 112(4): 654-659.
13.	MCMONNIES C W. Inflammation and keratoconus[J]. Optometry and Vision Science, 2015, 92(2): E35-E41.
14.	SOLOMON A, IVANIR Y, ORUCOV F, et al. Increased expression of inflammatory cytokines and cathepsins in the corneal epithelium in keratoconus[J]. Invest Ophthalmol Vis Sci, 2006, 47(13): 4380-4380.
15.	STRONGIN A Y, COLLIER I, BANNIKOV G, et al. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease[J]. J Biol Chem, 1995, 270(10): 5331-5338.
16.	CHENG F, LIU H, LUO X M, et al. Progress in the design of matrix metalloproteinase inhibitors[J]. Progress in Chemistry, 2001, 13(4): 283-293.
17.	MOORE C S, CROCKER S J. An alternate perspective on the roles of TIMPs and MMPs in pathology[J]. Am J Pathol, 2012, 180(1): 12-16.
18.	SMITH V A, MATTHEWS F J, MAJID M A, et al. Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation[J]. Biochim Biophys Acta, 2006, 1762(4): 431-439.
19.	PREDOVI AĆU J, BALOG T, MAROTTI T, et al. The expression of human corneal MMP-2, MMP-9, proMMP-13 and TIMP-1 in bullous keratopathy and keratoconus[J]. Coll Antropol, 2008, 32(Suppl 2): 15-19.
20.	IHALAINEN A, SALO T, FORSIUS H, et al. Increase in type I and type IV collagenolytic activity in primary cultures of keratoconus cornea[J]. Eur J Clin Invest, 1986, 16(1): 78-84.
21.	GENINA E A, BASHKATOV A N, KAMENSKIKH I D, et al. OCT/LCT monitoring the drug effect on the human cornea structure in vivo[J]. J of Biomedical Photonics&Eng, 2015, 1: 77-80.
22.	ROBERT L, LEGEAIS J M, ROBERT A M, et al. Corneal collagens[J]. Pathol Biol (Paris), 2001, 49(4): 353-363.
23.	MACKIEWICZ Z, MÄÄTTÄ M, STENMAN M, et al. Collagenolytic proteinases in keratoconus[J]. Cornea, 2006, 25(5): 603-610.
24.	DU Genlai, LIU Chengxing, LI Xiaona, et al. Induction of matrix metalloproteinase-1 by tumor necrosis factor-α is mediated by interleukin-6 in cultured fibroblasts of keratoconus[J]. Exp Biol Med (Maywood), 2016: 1535370216650940.
25.	WANG Yequan, TANG Zhenyu, XUE R, et al. Combined effects of TNF-α, IL-1β, and HIF-1α on MMP-2 production in ACL fibroblasts under mechanical stretch: an in vitro study[J]. J Orthop Res, 2011, 29(7): 1008-1014.
26.	SHINDO S, HOSOKAWA Y, HOSOKAWA I, et al. Genipin inhibits MMP-1 and MMP-3 release from TNF-a-stimulated human periodontal ligament cells[J]. Biochimie, 2014, 107(Pt B): 391-395.
27.	WANG Chenghu, CAO Guofan, JIANG Qin, et al. TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling[J]. Biochem Biophys Res Commun, 2012, 425(1): 33-38.
28.	HONG C S, FELLOWS W, NIRANJAN A, et al. Ectopic matrix metalloproteinase-9 expression in human brain tumor cells enhances oncolytic HSV vector infection[J]. Gene Ther, 2010, 17(10): 1200-1205.
29.	ROMERO-JIMÉNEZ M, SANTODOMINGO-RUBIDO J, WOLFFSOHN J S. Keratoconus: A review[J]. Contact Lens & Anterior Eye the Journal of the British Contact Lens Association, 2010, 33(4): 157-166.
30.	COLLIER S A, MADIGAN M C, PENFOLD P L. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and MMP-2 in normal and keratoconus corneas[J]. Curr Eye Res, 2000, 21(2): 662-668.
31.	STEENPORT M, KHAN K M, DU B, et al. Matrix metalloproteinase (MMP)-1 and MMP-3 induce macrophage MMP-9: evidence for the role of TNF-α and cyclooxygenase-2[J]. J Immunol, 2009, 183(12): 8119-8127.
32.	SHETTY R, GHOSH A, LIM R R, et al. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A[J]. Invest Ophthalmol Vis Sci, 2015, 56(2): 738-750.
33.	NAGASE H, WOESSNER J F. Matrix metalloproteinases[J]. Journal of Biological Chemistry, 1999, 274(31): 21491-21494.
34.	BI Hongxia, SHI Hanbing, ZHANG Ting, et al. PRDM14 promotes the migration of human non-small cell lung cancer through extracellular matrix degradation in vitro[J]. Chin Med J, 2015, 128(3): 373-377.

1. CHOPRA I, JAIN A K. Between eye asymmetry in keratoconus in an Indian population[J]. Clinical and Experimental Optometry, 2005, 88(3): 146-152.
2. ZADNIK K, STEGER M K, FINK B A, et al. Between-eye asymmetry in keratoconus[J]. Cornea, 2002, 21(7): 671-679.
3. WEED K H, MCGHEE C N, MACEWEN C J. Atypical unilateral superior keratoconus in young males[J]. Cont Lens Anterior Eye, 2005, 28(4): 177-179.
4. NIELSEN K, HJORTDAL J, PIHLMANN M, et al. Update on the keratoconus genetics[J]. Acta Ophthalmol (Copenh), 2013, 91(2): 106-113.
5. RABINOWITZ Y S. Keratoconus[J]. Surv Ophthalmol, 1998, 42(4): 297-319.
6. LEMA I, SOBRINO T, DURÁN J A, et al. Subclinical keratoconus and inflammatory molecules from tears[J]. Br J Ophthalmol, 2009, 93(6): 820-824.
7. POULIQUEN Y, BUREAU J, MIRSHAHI M, et al. Keratoconus and inflammatory processes[J]. Bulletin de la Société belge d'ophtalmologie, 1996, 262: 25-28.
8. YOON K C, JEONG I Y, PARK Y G, et al. Interleukin-6 and tumor necrosis factor-alpha levels in tears of patients with dry eye syndrome[J]. Cornea, 2007, 26(4): 431-437.
9. PRADA J, NOELLE B, BAATZ H, et al. Tumour necrosis factor alpha and interleukin 6 gene expression in keratocytes from patients with rheumatoid corneal ulcerations[J]. Br J Ophthalmol, 2003, 87(5): 548-550.
10. PANNEBAKER C, CHANDLER H L, NICHOLS J J. Tear proteomics in keratoconus[J]. Mol Vis, 2010, 16: 1949-1957.
11. BALASUBRAMANIAN S A, MOHAN S, PYE D C, et al. Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus[J]. Acta Ophthalmol (Copenh), 2012, 90(4): E303-E309.
12. LEMA I, DURÁN J A. Inflammatory molecules in the tears of patients with keratoconus[J]. Ophthalmology, 2005, 112(4): 654-659.
13. MCMONNIES C W. Inflammation and keratoconus[J]. Optometry and Vision Science, 2015, 92(2): E35-E41.
14. SOLOMON A, IVANIR Y, ORUCOV F, et al. Increased expression of inflammatory cytokines and cathepsins in the corneal epithelium in keratoconus[J]. Invest Ophthalmol Vis Sci, 2006, 47(13): 4380-4380.
15. STRONGIN A Y, COLLIER I, BANNIKOV G, et al. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease[J]. J Biol Chem, 1995, 270(10): 5331-5338.
16. CHENG F, LIU H, LUO X M, et al. Progress in the design of matrix metalloproteinase inhibitors[J]. Progress in Chemistry, 2001, 13(4): 283-293.
17. MOORE C S, CROCKER S J. An alternate perspective on the roles of TIMPs and MMPs in pathology[J]. Am J Pathol, 2012, 180(1): 12-16.
18. SMITH V A, MATTHEWS F J, MAJID M A, et al. Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation[J]. Biochim Biophys Acta, 2006, 1762(4): 431-439.
19. PREDOVI AĆU J, BALOG T, MAROTTI T, et al. The expression of human corneal MMP-2, MMP-9, proMMP-13 and TIMP-1 in bullous keratopathy and keratoconus[J]. Coll Antropol, 2008, 32(Suppl 2): 15-19.
20. IHALAINEN A, SALO T, FORSIUS H, et al. Increase in type I and type IV collagenolytic activity in primary cultures of keratoconus cornea[J]. Eur J Clin Invest, 1986, 16(1): 78-84.
21. GENINA E A, BASHKATOV A N, KAMENSKIKH I D, et al. OCT/LCT monitoring the drug effect on the human cornea structure in vivo[J]. J of Biomedical Photonics&Eng, 2015, 1: 77-80.
22. ROBERT L, LEGEAIS J M, ROBERT A M, et al. Corneal collagens[J]. Pathol Biol (Paris), 2001, 49(4): 353-363.
23. MACKIEWICZ Z, MÄÄTTÄ M, STENMAN M, et al. Collagenolytic proteinases in keratoconus[J]. Cornea, 2006, 25(5): 603-610.
24. DU Genlai, LIU Chengxing, LI Xiaona, et al. Induction of matrix metalloproteinase-1 by tumor necrosis factor-α is mediated by interleukin-6 in cultured fibroblasts of keratoconus[J]. Exp Biol Med (Maywood), 2016: 1535370216650940.
25. WANG Yequan, TANG Zhenyu, XUE R, et al. Combined effects of TNF-α, IL-1β, and HIF-1α on MMP-2 production in ACL fibroblasts under mechanical stretch: an in vitro study[J]. J Orthop Res, 2011, 29(7): 1008-1014.
26. SHINDO S, HOSOKAWA Y, HOSOKAWA I, et al. Genipin inhibits MMP-1 and MMP-3 release from TNF-a-stimulated human periodontal ligament cells[J]. Biochimie, 2014, 107(Pt B): 391-395.
27. WANG Chenghu, CAO Guofan, JIANG Qin, et al. TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling[J]. Biochem Biophys Res Commun, 2012, 425(1): 33-38.
28. HONG C S, FELLOWS W, NIRANJAN A, et al. Ectopic matrix metalloproteinase-9 expression in human brain tumor cells enhances oncolytic HSV vector infection[J]. Gene Ther, 2010, 17(10): 1200-1205.
29. ROMERO-JIMÉNEZ M, SANTODOMINGO-RUBIDO J, WOLFFSOHN J S. Keratoconus: A review[J]. Contact Lens & Anterior Eye the Journal of the British Contact Lens Association, 2010, 33(4): 157-166.
30. COLLIER S A, MADIGAN M C, PENFOLD P L. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and MMP-2 in normal and keratoconus corneas[J]. Curr Eye Res, 2000, 21(2): 662-668.
31. STEENPORT M, KHAN K M, DU B, et al. Matrix metalloproteinase (MMP)-1 and MMP-3 induce macrophage MMP-9: evidence for the role of TNF-α and cyclooxygenase-2[J]. J Immunol, 2009, 183(12): 8119-8127.
32. SHETTY R, GHOSH A, LIM R R, et al. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A[J]. Invest Ophthalmol Vis Sci, 2015, 56(2): 738-750.
33. NAGASE H, WOESSNER J F. Matrix metalloproteinases[J]. Journal of Biological Chemistry, 1999, 274(31): 21491-21494.
34. BI Hongxia, SHI Hanbing, ZHANG Ting, et al. PRDM14 promotes the migration of human non-small cell lung cancer through extracellular matrix degradation in vitro[J]. Chin Med J, 2015, 128(3): 373-377.

Journal of Biomedical Engineering

Effects of Tumor Necrosis Factor Alpha on the Expression of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in Keratoconus Fibroblasts

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content