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Shreyas Masters Thesis.pdf (3.03 MB)

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ACTIVATED NEUTROPHILS MEDIATE KIM-1 SHEDDING AND RENAL REMODELLING

Lingadahalli, Shreyas Vaman
http://rave.ohiolink.edu/etdc/view?acc_num=csu1368404728

Abstract Details

2013, Master of Science in Biology, Cleveland State University, College of Sciences and Health Professions.
Kidney performs a complex task of concentrating the urine, retention of salts and protein and excretion of metabolic toxins and by the virtue of its function, is always under the chemical stress and subject to constant tissue damage. Post injury, nephrons have the ability to regain their function by remodeling including, clearing of apoptotic and necrotic debris. Kidney Injury Molecule-1(KIM-1/TIM-1/HAVCR-1) is a phosphatidylserine receptor that recognizes the apoptotic bodies and directs them to the lysosomal degradation. KIM-1 a type I transmembrane glycoprotein, although not constitutively expressed, is expressed in injured epithelial cells. It is known that the extracellular domain is cleaved by, MMP-9 and MMP-3, and the cleaved protein can be detected in the urine, making it a sensitive and non-invasive biomarker of renal injury. In rat renal injury model we observed neutrophil infiltration at the site of injury. To understand the role of neutrophis and its relation to KIM-1, we hypothesized, activated neutrophils increases shedding of the KIM-1 extracellular domain via MMP activity and thus reducing the uptake and clearing of apoptotic bodies. The purpose of the study is to determine if activated neutrophils can cause KIM-1 shedding and identify the MMP involved in this cleavage. Immortalized human proximal tubular (HK2) cells were treated with supernatant from PAF (pro-inflammatory lipid) activated neutrophils. We observed an increase shedding of KIM-1 on treatment with activated neutrophil supernatant and that shedding was blocked after pretreatment of neutrophils with an MMP-9 inhibitor. Pretreatment with MMP-3 inhibitor did not show any change. We also found KIM-1 mediated uptake of apoptotic bodies is reduced after the KIM-1 ectodomain shedding .Our study suggests that activated neutrophils can cause KIM-1 shedding via MMP-9 that consequentially reduces the phagocytic activity of the epithelial cells and thus affect the kidney remodeling
Thomas McIntyre, PhD (Advisor)
Crystal Weyman, PhD (Committee Member)
Christine Moravec, PhD (Committee Member)
81 p.
Cellular Biology

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Citations

  • Lingadahalli, S. V. (2013). ACTIVATED NEUTROPHILS MEDIATE KIM-1 SHEDDING AND RENAL REMODELLING [Master's thesis, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1368404728

    APA Style (7th edition)

  • Lingadahalli, Shreyas. ACTIVATED NEUTROPHILS MEDIATE KIM-1 SHEDDING AND RENAL REMODELLING. 2013. Cleveland State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1368404728.

    MLA Style (8th edition)

  • Lingadahalli, Shreyas. "ACTIVATED NEUTROPHILS MEDIATE KIM-1 SHEDDING AND RENAL REMODELLING." Master's thesis, Cleveland State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=csu1368404728

    Chicago Manual of Style (17th edition)

csu1368404728
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© 2013, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.