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Gamma linolenic acid exerts anti-inflammatory and anti-fibrotic effects in diabetic nephropathy

Title
 Gamma linolenic acid exerts anti-inflammatory and anti-fibrotic effects in diabetic nephropathy 
Other Titles
 실험적 당뇨병성 신병증에서 gamma linolenic acid 가 염증반응 및 세포외 기질 축적에 미치는 영향 
Issue Date
2011
Publisher
 Graduate School, Yonsei University 
Description
Dept. of Medical Science/석사
Abstract
Background: Accumulating evidence suggests that an inflammatory mechanism contributes to the development and progression of diabetic nephropathy. Gamma linolenic acid (GLA), a member of polyunsaturated fatty acids (PUFAs), has been reported to have an anti-inflammatory effect by generating modulatory molecules for inflammatory responses. In addition, previous studies have demonstrated that GLA abrogates rheumatologic diseases and diabetic neuropathy via an anti-inflammatory mechanism. However, the effect of GLA on diabetic nephropathy has been largely unexplored.Purpose: This study was undertaken to investigate the effects of GLA on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions.Methods: In vivo, 32 Sprague-Dawley rats were injected either with diluent [n=16, control(C)] or streptozotocin intraperitoneally [n=16, diabetes(DM)], and 8 rats from control and diabetic groups were treated with evening primrose oil by gavage (450 mg/kg/day) for 3 months. In vitro, rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose (NG), NG+24.4 mM mannitol (NG+M), and 30 mM glucose (HG) with or without GLA (10 or 100 M). Real-time PCR and Western blot were performed for intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression, respectively. Immunohistochemical staining for ICAM-1 and FN, and Masson’s trichrome staining with renal tissue were also performed.Results: Twenty four-hour urinary albumin excretion was significantly increased in DM compared to C rats (p<0.05), and GLA treatment significantly reduced albuminuria in DM rats (p<0.05). ICAM-1, MCP-1, and FN mRNA and protein expression were significantly increased in DM compared to C kidney, and these increases were significantly abrogated by GLA treatment. In addition, the extent of glomerular and tubulointerstitial fibrosis assessed by Masson’s trichrome staining was significantly greater in DM relative to C kidney (p<0.005), and this change was significantly ameliorated by the administration of GLA (p<0.01). In vitro, GLA significantly inhibited the increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1.Conclusion: GLA attenuates not only inflammation via inhibiting enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in diabetic nephropathy.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/133444
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 석사
Yonsei Authors
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