Hemker, Shelby
(2020)
Hypoxia-induced microRNA-210 regulation of kidney development.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Intrauterine growth restriction is a common pregnancy complication that is thought to arise from fetal hypoxia and results in reduced nephron number. This decrease in the total amount of nephrons (which are the functional unit of the kidney) increases an affected individual’s lifelong risk for developing disease, such as hypertension and chronic kidney disease. However, the mechanisms by which fetal hypoxia affects kidney development are poorly understood. To address this, an unbiased RNA sequencing approach was utilized to identify miRNAs induced by hypoxia during kidney development, of which miR-210 was identified as the top hypoxia-induced miRNA. To further understand the functional role that miR-210 plays in regulating kidney development, a transgenic mouse line with a global miR-210 deletion was investigated. Interestingly, deletion of miR-210 resulted in a male-specific decrease in nephron number, which appears to be due to a combination of increased expression of lymphoid enhancer-binding factor-1 (an effector of Wingless-related integration site/β-catenin signaling) and caspase-8 associated protein 2 (effector of Fas cell surface death receptor-mediated apoptosis signaling). To understand how deletion of miR-210 affects kidney development in the setting of fetal hypoxia, embryonic mice were exposed to moderate intrauterine hypoxia. Embryos with the miR-210 deletion did not exhibit many differences to their wildtype littermates also exposed to hypoxia, except that they may have decreased ureteric bud branching. Further investigation into the mechanisms by which hypoxia-induced miR-210 impacts kidney development during normal and hypoxic kidney development would expand our understanding of how hypoxic signaling impacts fetal development and risk for developing kidney disease.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
6 April 2020 |
| Date Type: |
Publication |
| Defense Date: |
2 March 2020 |
| Approval Date: |
6 April 2020 |
| Submission Date: |
26 March 2020 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
151 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Pediatrics |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
hypoxia, miRNA, kidney, development |
| Date Deposited: |
06 Apr 2020 19:18 |
| Last Modified: |
06 Apr 2020 19:18 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38395 |
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