Thesis
Leptin: effect on transforming growth factor-b1 and vascular endothelial growth factor in glomerular endothelial cells in an in vitro model of diabetes
Master of Science (MS), Washington State University
2008
Handle:
https://hdl.handle.net/2376/105309
Abstract
Diabetes and obesity are powerful contributors to glomerulosclerosis and end stage renal disease (ESRD). They are characterized by extracellular matrix (ECM) protein deposition (fibrosis), resulting in glomerulosclerosis, basement membrane thickening, mesangial expansion, glomerular and renal hypertrophy, progressive renal dysfunction and, eventually, ESRD. Recently, the adipokine leptin was described as a possible link between obesity and the increased risk for ESRD. Vascular endothelial growth factor (VEGF) is also important in progression of glomerulosclerosis. Leptin, high glucose, and VEGF can each increase markers of fibrosis, including transforming growth factor-beta (TGF-[beta]), a known stimulator of fibrosis. Little is known about the effect of leptin on TGF-[beta]1 or VEGF in glomerular endothelial cells. HYPOTHESIS: Leptin will increase TGF-[beta]1 and VEGF concentration in an in vitro model of diabetes using rat glomerular endothelial cells (RGEC). METHODS: RGEC were exposed to increasing doses of leptin (0, 15, 25, 50,100 ng/mL) for 48h in either normal (5.55mM) or high (25mM) glucose. Media was sampled at 12, 24 and 48 hr and assayed for TGF-[beta]1 and VEGF by sandwich ELISA. Data were analyzed by univariate ANOVA and t-tests. RESULTS: Leptin, in combination with high glucose, caused a significant linear doserelated increase in TGF-[beta]1 supernatant concentration at 12 hr and 48 hr (p<0.05), but significantly decreased TGF-[beta]1 in supernatant from cells grown in normal glucose (p<0.05). High glucose increased VEGF protein concentration in supernatant at 48 hr (p<0.05). Leptin had no effect on VEGF in either normal or high glucose (p>0.05). CONCLUSIONS: Leptin may contribute to the excessive glomerular ECM deposition seen in diabetes by increasing TGF-[beta]1 production in the presence of a high glucose concentration. Glucose-induced increases in VEGF could enhance glomerulosclerosis due to the ability of VEGF to promote fibrosis
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Details
- Title
- Leptin
- Creators
- Matthew L. Halloran
- Contributors
- Emily Carolyn Johnson (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Identifiers
- 99900525010701842
- Language
- English
- Resource Type
- Thesis