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Walter, Debra Accepted Dissertation 5-10-18 Su 18.pdf (5.99 MB)
ETD Abstract Container
Abstract Header
Renal Consequences of Coxsackievirus Infection and Type 1 Diabetes in Non-obese Diabetic Mice
Author Info
Walter, Debra L.
ORCID® Identifier
http://orcid.org/0000-0003-0070-5708
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1526020616767063
Abstract Details
Year and Degree
2018, Doctor of Philosophy (PhD), Ohio University, Biological Sciences (Arts and Sciences).
Abstract
Diabetes is the leading cause of end stage renal disease (ESRD) in the United States; however, the ability to predict which diabetic patients will go on to develop ESRD is lacking. While both type 1 (T1D) and type 2 (T2D) diabetes result in kidney injury and can be induced by genetic and environmental components, patients with T1D have a higher risk of developing ESRD over their lifetime. Furthermore, the environmental component of T1D has been understudied when considering secondary consequences, such as ESRD. Non-obese diabetic (NOD) mice spontaneously develop T1D with age, which can be accelerated by coxsackievirus (CV) infection, making the NOD mouse an ideal model to study kidney injury resulting from autoimmune and viral triggers. Thus, this study evaluated kidney injury in response to virus infection (a known environmental initiator of T1D) and T1D, both alone and together, to identify a link between causative agent and onset/nature/extent of kidney injury resulting from each. The objectives of this project were to assess 1) acute and 2) chronic viral-induced kidney damage in NOD mice independent of the onset of diabetes and to 3) characterize early molecular and cellular features of the NOD mouse kidney in the presence of hyperglycemia (diabetes), viral infection, and a combination of both and correlate these with the type and severity of kidney damage. Results indicated that while CV infects the kidneys of NOD mice and elicits a pattern recognition receptor response, no immune response or cytotoxic effects were observed, and the infection persists for at least 14 days. Furthermore, NOD mice which were infected with CV and later developed T1D appeared to be moderately protected from kidney injury compared to CV infection or T1D alone. Renal gene expression signatures for each treatment were also developed and indicated that it is possible to distinguish kidney injury biomarkers based on causative agent of injury. Together, these data identified initial kidney gene expression changes in response to virus infection that may play a role in later ESRD. This project provided the first step towards developing distinct kidney injury signatures for each injury type (genetic and environmental) in diabetic patients that may one day help provide better therapeutic options and predictive measures for patients with T1D.
Committee
Karen Coschigano, Ph.D. (Advisor)
Kelly McCall, Ph.D. (Advisor)
Frank Schwartz, M.D. (Committee Member)
Ramiro Malgor, M.D. (Committee Member)
Pages
210 p.
Subject Headings
Biology
;
Cellular Biology
;
Molecular Biology
Keywords
Type 1 Diabetes
;
Diabetic Nephropathy
;
Virology
;
Coxsackievirus
;
Innate Immune Response
;
Nephropathy
;
Acute Kidney Injury
;
Chronic Kidney Disease
;
Non-obese Diabetic Mice
;
Kidney Injury Biomarkers
;
Kidney Disease
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Citations
Walter, D. L. (2018).
Renal Consequences of Coxsackievirus Infection and Type 1 Diabetes in Non-obese Diabetic Mice
[Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1526020616767063
APA Style (7th edition)
Walter, Debra.
Renal Consequences of Coxsackievirus Infection and Type 1 Diabetes in Non-obese Diabetic Mice.
2018. Ohio University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1526020616767063.
MLA Style (8th edition)
Walter, Debra. "Renal Consequences of Coxsackievirus Infection and Type 1 Diabetes in Non-obese Diabetic Mice." Doctoral dissertation, Ohio University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1526020616767063
Chicago Manual of Style (17th edition)
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Document number:
ohiou1526020616767063
Download Count:
188
Copyright Info
© 2018, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.