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Characterization of proteinase activation peptides and their potential as diagnostic markers of disease

Voeghtly, Laura Marie (2009) Characterization of proteinase activation peptides and their potential as diagnostic markers of disease. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Prostate cancer is the second leading cause of cancer death in men. While prostate specific antigen (PSA) is currently the best biomarker available, its use has many limitations. This study investigates the biosynthesis, secretion and activation of PSA. PSA is secreted as a pro enzyme containing a seven amino acid activation peptide (APLILSR). Because APLILSR is removed extracellularly in vivo, the hypothesis was tested that it may be detected in the blood or urine. Our data indicates that APLILSR is filtered from the bloodstream by the kidney, and is detectable in the urine of patients with prostate cancer, but not controls. Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease of unknown etiology. Matrix metalloproteinases (MMPs) are a family of proteinases that regulate extracellular matrix turnover and are believed to contribute to IPF. For this reason, the hypothesis that levels of MMP activation peptides will increase in patients with IPF was tested. To test these hypotheses, urine from mice were collected and an ELISA was used to quantify MMP activation peptides. These experiments show that the activation peptides of MMP-2, MMP-7, MMP-8 and MMP-9 are increased in mice with pulmonary fibrosis compared to control mice. The data also showed that that the activation peptides of MMP-2, MMP-7, and MMP-9 are increased in the urine of human patients with IPF compared to healthy controls. These data suggest that urine detection of MMP activation peptides is feasible and correlates with disease. Because urinary detection of the activation peptides of proteinases are indicative of proteinase activation in vivo, the new hypothesis that the accurate measurement of proteinase activation peptides will be relevant clinically arises, and that such measurements may aid in the diagnosis of disease and serve as a marker for following disease progression.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Voeghtly, Laura Marielmn20@pitt.eduLMN20
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKaminski, Naftalinak38@pitt.eduNAK38
Committee ChairOury, Tim Dtdoury@pitt.eduTDOURY
Committee MemberWells, Alanwellsa@upmc.eduAHW6
Committee MemberDay, Billybday@pitt.eduBDAY
Committee MemberChu, Charleen Tctc4@pitt.eduCTC4
Date: 22 October 2009
Date Type: Completion
Defense Date: 9 September 2009
Approval Date: 22 October 2009
Submission Date: 18 September 2009
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Cellular and Molecular Pathology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: activation peptide; idiopathic pulmonary fibrosis; mmp; prostate cancer; protease activation; psa
Other ID:, etd-09182009-151608
Date Deposited: 10 Nov 2011 20:02
Last Modified: 19 Dec 2016 14:37


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