Molecular analysis of glucose transporter in glomerular mesangial cells

科学研究費補助金研究成果報告書研究種目: 一般研究(C)研究期間: 1991～1992課題番号: 03671143研究代表者: 吉川 隆一（滋賀医科大学・医学部・助教授

A Role of Gene Expression of Aldose Reductase in the Development of Diabetic Complications

科学研究費補助金研究成果報告書研究種目: 一般研究(C)研究期間: 1989～1990課題番号: 01570634研究代表者: 吉川 隆一（滋賀医科大学・医学部・助教授

Molecular analysis of type IV collagen accumulation in diabetic nephropathy

科学研究費補助金研究成果報告書研究種目: 一般研究(C)研究期間: 1993～1994課題番号: 05670853研究代表者: 吉川 隆一（滋賀医科大学・医学部・助教授

15-Deoxy-Δ12,14-prostaglandin J2 inhibits IL-1β–induced cyclooxygenase-2 expression in mesangial cells

15-Deoxy-Δ12,14-prostaglandin J2 inhibits IL-1β–induced cyclooxygenase-2 expression in mesangial cells.BackgroundCyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, is induced in mesangial cells in response to proinflammatory cytokines. Recently, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the natural ligands of peroxisome proliferator-activated receptor γ (PPARγ), has been reported to have an anti-inflammatory effect. Therefore, we examined the effect of 15d-PGJ2 on COX-2 expression in cultured rat mesangial cells.MethodsMesangial cells were incubated with 15d-PGJ2 for 30 minutes and then exposed to interleukin-1β (IL-1β). The expression of COX-2 mRNA and proteins was determined by Northern blot and immunoblot analyses, respectively. Accumulation of prostaglandin E2 (PGE2) was measured by an enzyme-linked immunosorbent assay (ELISA). Activities of mitogen-activated protein kinases (MAPKs) were evaluated by an immunoblot analysis. DNA binding activities of activator protein-1 (AP-1) or nuclear factor-κB (NF-κB) were examined by an electrophoretic mobility shift assay (EMSA). The activities of PPAR responsive elements (PPRE) and COX-2 promoter were measured by a luciferase reporter assay.Results15D-PGJ2 significantly suppressed IL-1β–induced COX-2 expression and PGE2 production, but thiazolidinediones, synthetic PPARγ ligands, did not affect COX-2 expression. Moreover, the cells transfected with a PPRE luciferase reporter did not respond to 15d-PGJ2. IL-1β rapidly activated extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), which were involved in the up-regulation of COX-2 induction, but 15d-PGJ2 inhibited the activation of these kinases. 15d-PGJ2 inhibited the IL-1β–induced increase in binding activities of nuclear proteins to consensus AP-1 site and AP-1–like site of COX-2 promoter but not of NF-κB. IL-1β was unable to activate the COX-2 promoter when the AP-1–like site was mutated.ConclusionsThese data suggest that 15d-PGJ2 inhibits IL-1β–induced COX-2 expression, independent of PPARγ activation, by suppression of ERK and JNK pathways and AP-1 activation in mesangial cells. Thus, 15d-PGJ2 may play an important role in the negative feedback mechanism of COX-2 expression in renal inflammation and may be useful as an anti-inflammatory agent

不揮発性分子のレーザー蒸発/レーザー分光の装置開発

第4回分子科学討論会, 2010年9月14日-17日, 大阪大学豊中キャンパス(大阪), 4A1

Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

BACKGROUND: The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. CASE PRESENTATION: Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD). A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. CONCLUSION: Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully

Development of the treatment of diabetic nephropathy by targeting the TGF-β signaling

科学研究費補助金研究成果報告書研究種目: 基盤研究(B)研究期間: 2000～2002課題番号: 12470227研究代表者: 吉川 隆一（滋賀医科大学・学長）研究分担者: 羽田 勝計（滋賀医科大学・医学部・講師）研究分担者: 古家 大祐（滋賀医科大学・医学部・助手）研究分担者: 前川 聡（滋賀医科大学・医学部・助手

The molecular mechanism of increase of TGF-β expression in diabetic glomeruli

科学研究費補助金研究成果報告書研究種目: 基盤研究(B)研究期間: 1997～1999課題番号: 09470218研究代表者: 吉川 隆一（滋賀医科大学・医学部・教授）研究分担者: 羽田 勝計（滋賀医科大学・医学部・講師）研究分担者: 古家 大祐（滋賀医科大学・医学部・助手）研究分担者: 前田 士郎（滋賀医科大学・医学部・助手