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RelA as a Potential Regulator of Inflammation and Tissue Damage in Streptozotocin-Induced Diabetic STAT5 Knockout Mice

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2016, Bachelor of Science (BS), Ohio University, Biological Sciences.
Type 1 Diabetes (T1D) affects 1.25 million Americans, and that number is expected to increase to 5 million by 2050. Failure to properly control blood glucose levels in T1D can result in life-threatening side effects such as kidney damage, also known as diabetic nephropathy (DN), and end-stage renal disease (ESRD). As the incident rate of T1D continues to rise worldwide, understanding DN becomes more important. This can be accomplished by examining the molecular mechanisms of damage in DN. It has been shown that the loss of STAT5 in diabetic mice exacerbates diabetic kidney damage. In this study, we used pathway analysis software to analyze gene expression results previously obtained from a microarray experiment using this diabetic STAT5 knockout (DB SKO) mouse model. We found that expression of many immune system pathways was significantly altered in the kidneys of DB SKO mice, as compared to nondiabetic and wildtype control mice. A number of different immune cell functions were also predicted to be altered. The RelA gene encoding the p65 subunit of NF¿B was predicted to be a common or “master” regulator of many of the differentially expressed genes within our dataset. Using chromatin immunoprecipitation, we found altered numbers of p65-DNA binding interactions in the promoters of differentially expressed genes within the DB SKO kidney, again in comparison to the nondiabetic and wildtype control kidneys. Therefore, our analyses indicate that STAT5 may act through RelA to affect immune system signaling pathways, resulting in an increase in inflammation and tissue damage in the absence of STAT5.
Karen Coschigano, Ph.D. (Advisor)
83 p.

Recommended Citations

Citations

  • Holtzapple, E. R. (2016). RelA as a Potential Regulator of Inflammation and Tissue Damage in Streptozotocin-Induced Diabetic STAT5 Knockout Mice [Undergraduate thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461342848

    APA Style (7th edition)

  • Holtzapple, Emilee. RelA as a Potential Regulator of Inflammation and Tissue Damage in Streptozotocin-Induced Diabetic STAT5 Knockout Mice . 2016. Ohio University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461342848.

    MLA Style (8th edition)

  • Holtzapple, Emilee. "RelA as a Potential Regulator of Inflammation and Tissue Damage in Streptozotocin-Induced Diabetic STAT5 Knockout Mice ." Undergraduate thesis, Ohio University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461342848

    Chicago Manual of Style (17th edition)