Mechanisms for the Progression of Renal Disease - Fatty Acids as an Aggravating Factor and Fatty Acid Binding Protein as an Ameliorating Factor

肾病进展机制——脂肪酸作为加重因素和脂肪酸结合蛋白作为改善因素

• 批准号: 13671099
• 负责人: KIMURA Kenjiro
• 金额: $ 2.62万
• 依托单位: St. Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671099/
• 关键词: fatty acid binding protein; renal damage; proteinuria; proximal tubule; cultured tubular cells; transgenic mice; トランスジェニックスマウス

In order to clarify the pathogenesis of the tubulointerstitial damage by proteinuria, we performed the following experiments.Bovine serum albumin (BSA) was intraperitoneally injected for 2 weeks. Normal BSA induced remarkable tubulointerstitial damage, while defatted BSA did mild tubulointerstitial damage. The cultured proximal tubules similarly took normal BSA and defatted BSA into the cytoplasm. We established transgenic mice where human L-FABP was expressed in the proximal tubule. Intraperitoneal injection of normal BSA into the transgenic mice made severe tubulointerstitial damage and the expression of L-FABP was enhanced. Urinary excretion of L-FABP was increased. However, defatted BSA induced only mild tubulointerstitial damage. Neither the renal expression of L-FABP nor the urinary excretion of L-FABP was changed.In conclusion, fatty acid bound to albumin play an important role in the pathogenesis of the tubulointerstitial damage induced by proteinuria. Fatty acid stress to the proximal tubule increased the renal expression and urinary excretion of L-FABP.

为了阐明蛋白尿致肾小管间质损伤的发病机制，我们进行了以下实验：用牛血清白蛋白(BSA)进行2周的腹腔注射。正常BSA可引起明显的肾小管间质损伤，而脱脂BSA对肾小管间质损伤较轻。培养的近端小管同样摄取正常的BSA，并将BSA脱脂进入细胞质。我们建立了转基因小鼠，人L-FABP在近端小管表达。转基因小鼠腹腔注射正常牛血清白蛋白造成严重的肾小管间质损伤，L-FABP的表达增强。L-FABP的尿排出量增加。然而，脱脂BSA仅引起轻微的肾小管间质损伤。结论：白蛋白结合脂肪酸在蛋白尿致肾小管间质损伤的发病机制中起重要作用。近曲小管脂肪酸应激增加了L-FABP的肾脏表达和尿液排泄量。

项目成果

Kamijo A, Kimura K et al.: "Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage"Kidney International. 62. 1628-1637 (2002)

Kamijo A、Kimura K 等人：“与白蛋白结合的尿液游离脂肪酸会加重肾小管间质损伤”国际肾脏病杂志。

Kamijo A, Kimura K et al: "Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage"Kidney International. 62. 1628-1637 (2002)

Kamijo A、Kimura K 等人：“与白蛋白结合的尿液游离脂肪酸会加重肾小管间质损伤”国际肾脏病杂志。

上條敦子, 木村健二郎: "尿中肝臓型fatty acid binding protein (L-FABP)の意義"Annual Review腎臓2001(編集:伊藤克己、浅野泰、遠藤仁、御手洗哲也、東原英二). 53-57 (2001)

Atsuko Kamijo、Kenjiro Kimura：“尿肝型脂肪酸结合蛋白 (L-FABP) 的意义”年度回顾肾脏 2001（编辑：Katsumi Ito、Yasushi Asano、Hitoshi Endo、Tetsuya Mitarai、Eiji Higashihara）53-57（ 2001）

上條敦子, 木村健二郎: "尿中肝臓型fatty acid binding Protein(L-FABP)の意義"Annual Review 腎臓 2001(編集:伊藤克己, 浅野泰, 遠藤仁,御手洗哲也, 東原英二). 53-57 (2001)

Atsuko Kamijo、Kenjiro Kimura：“尿肝型脂肪酸结合蛋白 (L-FABP) 的意义”年度回顾肾脏 2001（编辑：Katsumi Ito、Yasushi Asano、Hitoshi Endo、Tetsuya Mitarai、Eiji Higashihara）53-57（ 2001）

Kamijo A, Kimura K et al.: "Urinary Fatty Acids Bound to Albumin is an Aggravating Factor For the Tubulointerstitial Damage in Chronic Renal Disease"Journal of American Society of Nephrology. 12・(Abstract Issue). 680A (2001)

Kamijo A、Kimura K 等人：“与白蛋白结合的尿脂肪酸是慢性肾病肾小管间质损伤的加重因素”美国肾病学会杂志 12·（摘要期）680A。