title: Testican-1 promotes resistance against Pseudomonas aeruginosa-induced keratitis through regulation of MMP-2 expression and activation.
abstract: OBJECTIVE
  Testican-1 (or SPOCK) is a highly conserved chimeric proteoglycan encoded by the SPOCK1 gene. Protease regulatory activity has recently been demonstrated by this molecule and its family members testican-2 and -3. The present study tested the hypothesis that testican-1 regulates corneal matrix metalloproteinase (MMP)-2 expression, thus improving disease outcome after Pseudomonas aeruginosa-induced keratitis.
  
  
  METHODS
  C57BL/6 (B6) and BALB/c mice were routinely infected with P. aeruginosa and were evaluated at various postinfection (pi) times for corneal expression of testican-1 and MMP-2, by PCR array, real-time RT-PCR, ELISA, activity assays, zymography, and immunohistochemistry. Next, B6 mice were treated with recombinant human (rh) testican-1, and expression was knocked down in BALB/c ice by siTestican-1 treatment, to determine the relationship between the two molecules.
  
  
  RESULTS
  BALB/c versus B6 mice expressed significantly higher mRNA and protein levels of testican-1 after P. aeruginosa-induced ocular infection. MMP-2 expression and activation was also disparate between the two mouse strains. After rhTestican-1 treatment in B6 mice, overall disease response was significantly improved, whereas siRNA treatment of BALB/c mice converted the normally resistant response to susceptible. Testican-1 was shown to influence MMP-2 expression, activation, and regulation, as well.
  
  
  CONCLUSIONS
  This study demonstrates corneal expression of testican-1 and its temporal regulation of MMP-2 expression and activation after induction of bacterial keratitis. Furthermore, the data collectively indicate that testican-1 is a novel target for disease treatment to promote better disease outcome regarding chronic inflammation and infection and diseases involving pathologic tissue destruction.
authors: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. eberger@med.wayne.edu
authors: Elizabeth A
authors: EA
authors: Berger
authors: Sharon A
authors: SA
authors: McClellan
authors: Ronald P
authors: RP
authors: Barrett
authors: Linda D
authors: LD
authors: Hazlett
references: Biochem J. 1992 Dec 1;288 ( Pt 2):565-9
references: 1463459
references: Blood. 2002 Aug 15;100(4):1160-7
references: 12149192
references: Cancer Sci. 2007 Apr;98(4):563-8
references: 17425593
references: Prog Retin Eye Res. 2002 Jan;21(1):1-14
references: 11906808
references: Science. 1999 Oct 1;286(5437):113-7
references: 10506557
references: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):737-42
references: 19171647
references: Invest Ophthalmol Vis Sci. 2006 Jan;47(1):256-64
references: 16384971
references: Matrix Biol. 2006 Aug;25(6):373-81
references: 16806869
references: Ann Rheum Dis. 2003 Nov;62 Suppl 2:ii43-7
references: 14532148
references: Biochim Biophys Acta. 2005 May 25;1755(1):37-69
references: 15907591
references: J Immunol. 2000 Jun 15;164(12):6576-82
references: 10843717
references: Dev Genes Evol. 2003 Sep;213(9):456-63
references: 12898250
references: J Immunol. 2007 Jan 15;178(2):1105-14
references: 17202374
references: Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4360-7
references: 17724228
references: Invest Ophthalmol Vis Sci. 2007 May;48(5):2050-61
references: 17460260
references: Physiol Rev. 2007 Jan;87(1):69-98
references: 17237343
references: J Biol Chem. 1996 Feb 23;271(8):4373-80
references: 8626787
references: Br J Cancer. 2003 Nov 17;89(10):1817-21
references: 14612884
references: Genes Dev. 2000 Sep 1;14(17):2123-33
references: 10970876
references: Eur J Biochem. 2003 Sep;270(18):3739-49
references: 12950257
references: Prog Retin Eye Res. 2004 Jan;23(1):1-30
references: 14766315
references: Cancer Res. 2003 Jun 15;63(12):3364-9
references: 12810672
references: Matrix Biol. 2003 May;22(3):259-66
references: 12853036