S100A8 and A9 proteins regulate expression of key genes for inflammation and wound healing.
Khoo, Jasmine Ser Chin.
Date of Issue2013
School of Biological Sciences
Singapore Eye Research Institute
Pterygium is a common ocular surface disease characterized by centripetal invasion of the conjunctival epithelium onto the cornea. The disease has a wing-shaped phenotype accompanied by inflammatory infiltrate and accumulation of proteases and extracellular matrix components. S100A proteins are involved in activating the immune system, and previous studies have implicated S100A8/A9 in many ocular surface diseases such as meibomian gland dysfunction, dry eye, preservative induced epitheliopathy and chemical injury. Since a variety of matrix and inflammatory proteins are dysregulated in pterygium, in this thesis, I attempt to determine if S100A protein is a master regulator that triggers these changes by adding S100A8, A9 and heterocomplex S100A8/A9 to cultured conjunctival fibroblasts. A variety of transcript changes were examined. Inflammatory chemokine (Chemokine (C-X-C motif) ligand 1), matrix proteins (Vimentin, Biglycan, and Gelsolin), Annexin-A2, Thymosin beta-4 and Ras-related protein Rab 10 molecules known to be upregulated in pterygium, were found to be induced by S100A8, A9 and A8/A9.These genes are therefore possible downstream of S100A8/A9 in diseases. Chymase-1 and Serpin peptidase inhibitor, clade A member 1 (SERPINA1) are known to be downregulated in pterygium but are upregulated by S100A9 protein, suggesting presence of other disease pathways. Intervention in S100A proteins may be impactful on a wide variety of ocular surface diseases by reducing disease mediators.
Final Year Project (FYP)
Nanyang Technological University