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Shungang Zhang_Dissertation.pdf (3.65 MB)

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Disruption of Cd40 Attenuates Renal Injury and Improves Renal Function Following Experimental Renal Ischemia

Zhang, Shungang
http://rave.ohiolink.edu/etdc/view?acc_num=mco1596812338615142

Abstract Details

2020, Doctor of Philosophy (PhD), University of Toledo, Biomedical Sciences (Molecular Medicine).
Chronic kidney disease is the progressive loss of kidney function, which is prevalent in up to 13% of the global population and has become a major health burden. As the loss of function advances, complete loss of kidney function progresses to kidney failure, or end-stage renal disease (ESRD). Each kidney contains heterogeneous cell types and renal dysfunction is correlated with a complication of various characteristics such as proteinuria, renal fibrosis, tubular injury, inflammation and glomerular alterations. Renal ischemia is a common cause that contributes to the development of chronic kidney disease. CD40 was found to be a factor associated with immune responses and involved in the process of developing renal fibrosis. It has been reported that the disruption of Cd40 gene was sufficient to alleviate renal injury and rescued renal function in the hypertensive salt-sensitive Dahl S rats. The goal of my dissertation is to illustrate the effects of disrupting Cd40 in the settings of experimental renal ischemia in the rat model as well as identifying the potential targets of CD40 signaling and the underlying mechanisms by which they are regulated to contribute to the progression of renal disease. Specifically, Goldblatt two-kidney one clip (2K1C) surgery was performed on hypertensive Dahl salt-sensitive rats (S rats) and genetically modified S rats in which CD40 function is abolished (Cd40mutant). The well accepted Goldblatt two kidney, one clip model introduced renal ischemia and I demonstrated disruption of Cd40 significantly reduced renal fibrosis. Reciprocal kidney transplantation provided evidence that renal expression of CD40 specifically contributed to the development of renal fibrosis. Also, we identified matrix metalloproteinase-9 (MMP-9) as a downstream target regulated by CD40 signaling in renal proximal tubule epithelial cells. CD40 signaling also contributed to tubular cell death in the model of acute high salt-induced renal injury.
Steven Haller (Committee Chair)
David Kennedy (Committee Member)
Stanislaw Stepkowski (Committee Member)
Randall Worth (Committee Member)
Deepak Malhotra (Committee Member)
111 p.
Biomedical Research

Recommended Citations

Citations

  • Zhang, S. (2020). Disruption of Cd40 Attenuates Renal Injury and Improves Renal Function Following Experimental Renal Ischemia [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1596812338615142

    APA Style (7th edition)

  • Zhang, Shungang. Disruption of Cd40 Attenuates Renal Injury and Improves Renal Function Following Experimental Renal Ischemia. 2020. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1596812338615142.

    MLA Style (8th edition)

  • Zhang, Shungang. "Disruption of Cd40 Attenuates Renal Injury and Improves Renal Function Following Experimental Renal Ischemia." Doctoral dissertation, University of Toledo, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=mco1596812338615142

    Chicago Manual of Style (17th edition)

mco1596812338615142
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.