Date of Graduation
Master of Science in Cell and Molecular Biology
renal fibrosis, homotrimeric type I collagen, Col1a2-deficient mouse model, platelet derived growth factor, glomeruli, secondary wound healing
Animal Diseases | Animals | Diseases | Medicine and Health Sciences | Physiological Processes | Reproductive and Urinary Physiology
Progressive accumulation of collagen and extracellular matrix (ECM) proteins within renal glomeruli have implications for or result in renal fibrosis and glomerulosclerosis, with both events culminating in renal failure. To model this accumulation the Col1a2-deficient mouse model was used. The Col1a2-deficientmouse model is characterized by a mutation in the a2(I) chain, preventing incorporation into the type I collagen molecule. As a result, an α1(I) collagen chain incorporates into the collagen triple helix forming homotrimeric type I collagen, as opposed to heterotrimeric type I collagen. This change is due to the secondary wound healing response in response to ECM accumulation, fibrosis, or damage. Transforming growth factor-beta (TGF-β) has been studied within this model and demonstrated it was not the initiating molecule in collagen deposition. This study looks at Tumor Necrosis Factor-Alpha (TNF-a) and Platelet Derived Growth Factor (PDGF) as potential mediators of this hypothesized secondary wound healing response. TNF-ais an inflammatory cytokine produced following tissue damage, released by mesangial cells, and has been shown to induce epithelial-to-mesenchymal transition (EMT). Recently, PDGF receptors and ligand upregulation has been shown in other mouse models of renal fibrosis. However, TNF-ashowed no differential staining upon Picrosirius Red (PSR) between experimental and control groups. PDGFR-ββ and PDGF-BB displayed differential labeling in Col1a2-deficient in comparison to age matched wild type animals. The results for PDGF-DD mice were less conclusive when comparing the Col1a2-deficient mice to that of their wild type counterparts.
© Isaac C. Springer
Springer, Isaac C., "Investigation into the Role of Platelet Derived Growth Factor (PDGF) in Type I Collagen Glomerulopathy" (2018). MSU Graduate Theses. 3273.