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Title: Mesangial cell matrix deposition in high glucose as a model of glomerulosclerosis
Authors: Miller, Charles Grabel
Advisors: Schwarzbauer, Jean E
Contributors: Molecular Biology Department
Keywords: Collagen
Subjects: Cellular biology
Molecular biology
Issue Date: 2014
Publisher: Princeton, NJ : Princeton University
Abstract: The filtration unit of the kidney is the glomerulus, a capillary network supported by mesangial cells and their extracellular matrix (ECM). Glomerular function is compromised in diabetic nephropathy (DN) by uncontrolled buildup of ECM components, especially collagen IV, which progressively occlude the capillaries. Increased levels of the ECM protein fibronectin (FN) are also present at early stages of DN, however its role is unknown. Mesangial cells cultured under high glucose conditions provide a model system for studying the effect of elevated glucose levels on deposition of FN and type IV collagen, the predominant ECM component of glomerular lesions. Quantitative imaging of mesangial cell cultures and analysis of detergent-insoluble matrix showed that high glucose induced mesangial cells to assemble significantly more FN matrix, independent of FN protein levels. Mn2+-induced activation of integrins stimulated FN assembly in normal glucose, suggesting that high glucose affects integrin activity. Collagen IV matrix was also increased and co-localized with FN fibrils. An inhibitor of FN matrix assembly also prevented collagen IV deposition, demonstrating the dependence of collagen IV on FN matrix. We conclude that high glucose induces FN assembly, which contributes to collagen IV accumulation. Enhanced assembly of FN might facilitate dysregulated ECM accumulation in DN.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Molecular Biology

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