Analysis of GCIP Function in Rheumatoid Arthritis
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Date
2024-04-29
Authors
Nessipbekova, Assem
Journal Title
Journal ISSN
Volume Title
Publisher
Nazarbayev University School of Medicine
Abstract
The global burden of rheumatoid arthritis (RA) is increasing for the ageing population. The
disease is characterized by progressive joint inflammation and tissue destruction. One of the key players in the pathogenesis of RA is synovial fibroblasts (SF), which invade and destroy the cartilage in the joints. However, the exact molecular mechanism which explains their abnormal
outgrowth is yet to be elucidated. Grap2 cyclin D interacting protein (GCIP), a protein related to Id proteins, plays a role in cell cycle progression and gene expression by blocking interactions between (CREB) binding protein (CBP) and RNA polymerase II complexes. A recent study has shown that Grap2 cyclin D interacting protein (GCIP) has been downregulated in the synovial fibroblasts in rheumatoid arthritis patients, suggesting its involvement in disease progression.
The knockdown of the GCIP protein resulted in the increased growth of synovial fibroblasts, consequently leading to the upregulation of Cyclin D1, a crucial cell cycle and cell proliferation player regulated by the CREB.
This thesis aimed to explore the role of GCIP in the pathogenesis of rheumatoid arthritis by
establishing a mouse model of rheumatoid arthritis and testing how GCIP knockout affects the proliferation of synovial fibroblast during RA. Two cohorts of WT and GCIP KO C57BL/6 mice were utilized to induce RA with 2 different protocols. The protocol 2 resulted in a more pronounced disease phenotype in males. Female mice from both showed no visible signs of RA.
The role of GCIP on the proliferation of the synovial fibroblasts was not established
necessitating a larger cohort size and choosing male mice as a subject.
Description
Keywords
Type of access: Restricted, rheumatoid arthritis, synovial fibroblasts, GCIP
Citation
Nessipbekova, Assem. (2024) Analysis of GCIP Function in Rheumatoid Arthritis. Nazarbayev University School of Medicine