Mohd Nawi, Norfazlina;
(2025)
Studying the Links Between the Loss of POU4F2/BRN-3B and Inflammatory Changes that Contribute to Cardiovascular Disease.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Mohd Nawi_10205715_DAF_sig-removed.pdf Download (11MB) | Preview |
Abstract
Chronic diseases such as cardiovascular disease (CVD) and Type 2 Diabetes Mellitus (T2DM) are intricately linked to inflammatory responses, with gene expression changes governed by transcription factors playing a crucial role. This thesis delves into the potential association between the Brn-3b transcription factor and inflammatory response, and its possible link to vascular dysfunction. Initial investigations utilizing human THP-1 and Jurkat cells unveiled an upregulation of Brn-3b protein post-vitamin D3 treatment in THP-1 cells and in PMA+IL4 differentiated THP-1 cells, contrasting with non-significant changes in activated and non-activated human Jurkat cells. Employing a Brn-3b knock-out (Brn-3b KO) mouse model, I observed that the cellular immune cell profile, specifically CD44- immune-related cells in T and non-T cell lineages including monocytes, B lymphocytes, and granulocytes in Brn-3b KO bone marrow and blood, did not significantly change compared to wild-type (WT) controls. Furthermore, I explored the inflammatory status of the Brn-3b KO mouse model by analysing soluble protein mediators in bone marrow conditional medium and blood plasma. The data showed no significant alteration of protein biomarkers tumor necrosis factor alpha (TNFα), IL-1β, and IL-6 in bone marrow supernatant, while interestingly, IL-1β was significantly reduced in Brn-3b KO blood plasma, but not TNFα and IL-6. In the final chapter, I investigated the potential link between immune response and alterations in vascular proteins in the aorta of Brn-3b KO mice. The analysis showed no significant changes in immune markers (CD3, CD45R/B220, CD11b, CD44) or vascular proteins (alpha smooth muscle actin (αSMA), smooth muscle protein 22 (SM22)) and proliferative marker Ki67 in Brn-3b KO samples. An additional work on spleen also showed these immune markers CD3, CD4, CD8, CD44, CD11b, B220 and Thy-1 in Brn-3b KO mice mirrored those in WT controls. Overall, the findings suggest that the loss of Brn3b may not substantially impact immune regulatory responses in bone marrow, blood, aorta, and spleen tissue of the Brn-3b KO mouse model.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Studying the Links Between the Loss of POU4F2/BRN-3B and Inflammatory Changes that Contribute to Cardiovascular Disease |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | T2DM, CVD, Transcription Factors, Brn-3b, Inflammation, Vascular Dysfunction, Bone Marrow (BM) |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10205715 |
Archive Staff Only
 |
View Item |
