Date of Graduation
Master of Science in Cell and Molecular Biology
The progressive accumulation of collagen and other extracellular matrix proteins in the renal mesangium results in fibrosis, glomerulosclerosis, and eventual renal failure. Mice deficient in integrating α2(I) collagen into the type I collagen structure, termed Col1a2-deficient mice, model kidney fibrosis through the condition Type I Collagen Glomerulopathy, because homotrimeric type I collagen accumulates extracellularly in the mesangium of renal glomeruli. Accumulation of homotrimeric type I collagen compresses blood vessels in glomeruli, which reduces filtration, increases pressure, and results in fibrosis. Picrosirius red (PSR) staining was used on Col1a2 deficient and wildtype mice to evaluate collagen deposition. Histological evaluation and lesion scoring of kidney sections demonstrates that in comparison to wild-type mice, Col1a2-deficient homozygous mice exhibit abnormal glomerular collagen deposition. Immunohistochemistry (IHC) was then used to explore initiating factors of the Type I Collagen Glomerulopathy in Col1a2 deficient and healthy mice. Platelet-derived growth factors (PDGFs) contribute to wound healing, differentiating blood and vascular tissues, repairing blood vessels, and growth of mesenchymal cells. PDGF isoforms are commonly involved in fibrosis, especially in kidneys. Using IHC, PDGF-B and PDGF-D were used to explore a relationship between Type I Collagen Glomerulopathy and these isoforms. PDGF-B was found in glomeruli and tubules of diseased tissues, while PDGF-D was only found in tubules of diseased kidneys. This relationship between PDGF-B and glomerulopathy could lead to therapeutic developments to block the deposition of collagen and limit the progression of conditions that result in renal fibrosis.
collagen, extracellular matrix, fibrosis, homotrimeric, Type I Collagen Glomerulopathy, platelet-derived growth factor
Cell Biology | Molecular Biology
© Matthew James Freese
Freese, Matthew James, "Further Investigation of the Initiating Mechanism of the Type I Collagen Glomerulopathy" (2022). MSU Graduate Theses. 3758.