Role of Nudt21 Mediated Alternative Polyadenylation and Hyaluronan In The Development of Pulmonary Hypertension

<p>Pulmonary hypertension (PH) is a progressive disease with serious effects on quality of life and life expectancy of patients. PH is a complex disease that likely develops due to multiple influences, and no curative treatments exist for this disease. It has been shown that alternative polyadenylation (APA) due to depletion of Nudix Hydrolase 21(NUDT21) is involved in several disease states including the chronic lung disease idiopathic pulmonary fibrosis (IPF). Additionally, hyaluronan, an extracellular matrix glycosaminoglycan has been associated with PH. The role and mechanism of NUDT21 and hyaluronan have not yet been described in this disease. My results reveal that NUDT21 depletion and APA in pulmonary artery smooth muscle cells (PASMCs) is associated with phenotypic changes and PH. I I also show that hyaluronan and hyaluronan related genes play important roles in the development of Pulmonary Arterial Hypertension (PAH) and PH associated with IPF and combined pulmonary fibrosis and emphysema. I also identify 4-methylumbelliferone as an inhibitor of PH in this mechanism. These studies provide new mechanisms for understanding the development of PH and potential therapeutic targets.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2019

Authors dc:creator

• Collum, Scott Dale
• <p>0000-0001-5510-7356</p>

Contributors dc:contributor

• Harry Karmouty-Quintana, Ph.D.
• Darren F. Boehning, Ph.D
• Seyed J. Moghaddam, M.D.

• Pulmonary Hypertension
• Alternative Polyadenylation
• APA
• Hyaluronan
• HAS2
• Combined Pulmonary Fibrosis and Emphysema
• CPFE
• HA
• Medicine and Health Sciences
• Respiratory Tract Diseases

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/962

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2009