Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function
ER stress is associated with beta-cell dysfunction in Type 2 diabetes (T2D). A recent study by Dorajoo and colleagues show that several ER stress implicated genes including HSP90B1, DNAJC3, UCHL1 are upregulated in pancreatic islets from Singaporean-Chinese donors. Besides these genes, OLMALINC,...
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| Format: | Final Year Project (FYP) |
| Language: | English |
| Published: |
2018
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| Online Access: | http://hdl.handle.net/10356/74672 |
| _version_ | 1826119951982788608 |
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| author | Tan, Patricia Yan Dan |
| author2 | Yusof Ali |
| author_facet | Yusof Ali Tan, Patricia Yan Dan |
| author_sort | Tan, Patricia Yan Dan |
| collection | NTU |
| description | ER stress is associated with beta-cell dysfunction in Type 2 diabetes (T2D). A recent
study by Dorajoo and colleagues show that several ER stress implicated genes
including HSP90B1, DNAJC3, UCHL1 are upregulated in pancreatic islets from
Singaporean-Chinese donors. Besides these genes, OLMALINC, a lincRNA with
unknown function in beta-cells, was upregulated. We thus explored the effect of
OLMALINC knockdown (KD) on expression of ER stress-related and beta-cell
signature genes, under both normal and ER stress conditions. A second gene,
ERO1β, shown to be important in mediating ER stress responses and beta-cell
function in murine cell lines and mouse models, was also studied in the context of
human beta-cells under normal and ER stress conditions. Our results show that
OLMALINC KD had no significant impact on either beta-cell function or beta-cell
responsiveness to heightened ER stress, suggesting that OLMALINC does not play
a role in ER stress or significantly impact beta-cell identity and function. In contrast,
ERO1β KD induced critical ER stress-related gene expression under ER stress
conditions, corroborating murine models that ERO1β significantly impacted beta-cells
responsiveness to ER stress. However, this effect was not seen in normal, nonER
stress conditions. Our results propose that ERO1β downregulation in beta-cells
may exacerbate ER stress, promote beta-cell dysfunction and thereby drive T2D
pathogenesis. |
| first_indexed | 2024-10-01T05:08:33Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/74672 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:08:33Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/746722023-02-28T18:06:40Z Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function Tan, Patricia Yan Dan Yusof Ali School of Biological Sciences DRNTU::Science::Biological sciences ER stress is associated with beta-cell dysfunction in Type 2 diabetes (T2D). A recent study by Dorajoo and colleagues show that several ER stress implicated genes including HSP90B1, DNAJC3, UCHL1 are upregulated in pancreatic islets from Singaporean-Chinese donors. Besides these genes, OLMALINC, a lincRNA with unknown function in beta-cells, was upregulated. We thus explored the effect of OLMALINC knockdown (KD) on expression of ER stress-related and beta-cell signature genes, under both normal and ER stress conditions. A second gene, ERO1β, shown to be important in mediating ER stress responses and beta-cell function in murine cell lines and mouse models, was also studied in the context of human beta-cells under normal and ER stress conditions. Our results show that OLMALINC KD had no significant impact on either beta-cell function or beta-cell responsiveness to heightened ER stress, suggesting that OLMALINC does not play a role in ER stress or significantly impact beta-cell identity and function. In contrast, ERO1β KD induced critical ER stress-related gene expression under ER stress conditions, corroborating murine models that ERO1β significantly impacted beta-cells responsiveness to ER stress. However, this effect was not seen in normal, nonER stress conditions. Our results propose that ERO1β downregulation in beta-cells may exacerbate ER stress, promote beta-cell dysfunction and thereby drive T2D pathogenesis. Bachelor of Science in Biological Sciences 2018-05-23T02:06:30Z 2018-05-23T02:06:30Z 2018 Final Year Project (FYP) http://hdl.handle.net/10356/74672 en Nanyang Technological University 36 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Tan, Patricia Yan Dan Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function |
| title | Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function |
| title_full | Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function |
| title_fullStr | Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function |
| title_full_unstemmed | Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function |
| title_short | Knockdown of two ER stress-related genes and their effect on pancreatic beta-cell function |
| title_sort | knockdown of two er stress related genes and their effect on pancreatic beta cell function |
| topic | DRNTU::Science::Biological sciences |
| url | http://hdl.handle.net/10356/74672 |
| work_keys_str_mv | AT tanpatriciayandan knockdownoftwoerstressrelatedgenesandtheireffectonpancreaticbetacellfunction |