Mesangial cell regulation under the over expression of oxygen radical scavengers

氧自由基清除剂过度表达下的系膜细胞调节

• 批准号: 12671056
• 负责人: YAMADA Harutaka
• 金额: $ 1.09万
• 依托单位: Aichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671056/
• 关键词: superoxide dismutase; oxygen radicals; nephritis; mesangial cell; gene regulation; differentiation; Superoxide Dismutase; Mesangial Cell; Oxygen Radical Species; Monoclonal Antibody; Oxygen Radical species

The kidney glomerular mesangial cells (MCs) are mesenchymally derived cell in a pivotal position to induce the oxygen radical injury through the cytokines production, which is the clinical target for glucocorticoid treatment in glomerular nephritis. In culture condition, MC shows exert several action including the oxygen radical and chemokine production by glucocorticoid or phorbol myristate acetate (PMA) stimulation. According to the modification of MC differentiation; experimental nephritis, immune-complex, EC-SOD production of MC, which is the important for reduction of oxygen radical toxity in extracellular space, was assessed through the cAMP and chemokine production. EC-SOD production of MC was recognized in early stage, and continues to stable in confluent state. The correlation of MC differentiation marker, oxygen radical production oxygenradical scavengers, EC-SOD production was positively correlated with MCs differentiation, negatively correlated with oxygen radical production. Among the ten cases, the glucocorticoid stimulation which induce the stable condition of MC, enhance the both of EC-SOD and cAMP production, suppress the IL-6 and IL-8 production in dose dependent manner. In contrast, PMA stimulation, which induce the activation of mesangial cell, enhance the both of the IL-6 and IL-8 production, suppress the EC-SOD and cAMP production. In unstimulat condition, EC-SOD production was positively correlated with cAMP content, negatively correlated with IL-6 and IL-8 production. The enhancement of the EC-SOD production in MC associate with the promotion of the cAMP production, result in the suppression of IL-6 and IL-8 production, may play the pathophisiological role of glomerular nephritis, suggest the one of the pharmacological activities in glucocorticoid.

肾小球系膜细胞（MCs）是间充质来源的细胞，在通过产生细胞因子诱导氧自由基损伤中处于关键地位，是糖皮质激素治疗肾小球肾炎的临床靶点。在培养条件下，MC表现出多种作用，包括通过糖皮质激素或肉豆蔻酸佛波醇乙酸酯(PMA)刺激产生氧自由基和趋化因子。根据MC分化修饰；通过cAMP和趋化因子的产生来评估实验性肾炎、免疫复合物、MC的EC-SOD产生，这对于减少细胞外空间中的氧自由基毒性很重要。 MC的EC-SOD产生在早期就被识别出来，并在汇合状态下继续稳定。 MC分化标志物、氧自由基产生量、氧自由基清除剂、EC-SOD产生量的相关性与MCs分化呈正相关，与氧自由基产生呈负相关。 10例中，糖皮质激素刺激可诱导MC病情稳定，同时增强EC-SOD和cAMP的产生，并以剂量​​依赖性方式抑制IL-6和IL-8的产生。相反，PMA刺激可诱导系膜细胞活化，增强IL-6和IL-8的产生，抑制EC-SOD和cAMP的产生。在未刺激条件下，EC-SOD的产生与cAMP含量呈正相关，与IL-6和IL-8的产生呈负相关。 MC中EC-SOD产生的增强与cAMP产生的促进有关，导致IL-6和IL-8产生的抑制，可能在肾小球肾炎的病理生理学中发挥作用，提示其为糖皮质激素的药理活性之一。

项目成果

Yamada H, Adachi T, Fukatsu A, Misao S, Yamada Y, Aoki T, Miura N, Sakuma M, Nishikawa K, Futenma A, Kakumu S.: "Extracellular superoxide dismutase and glomerular mesangial cells : Its production and regulation"Nephrology. 26・5. 95-96 (2002)

Yamada H、Adachi T、Fukatsu A、Misao S、Yamada Y、Aoki T、Miura N、Sakuma M、Nishikawa K、Futenma A、Kakumu S.：“细胞外超氧化物歧化酶和肾小球系膜细胞：其产生和调节”肾脏病学。 26・5。95-96（2002）

山田晴生,三浦直人,青木隆成,田中芳徳,楊朝隆,佐久間正人,原努,宮井宏暢,深津敦司,普天間新生,各務伸一,足立哲夫,山田裕一: "腎とフリーラジカル-Extracellular Superoxide Dismutase(EC-SOD)の遺伝的多型性-"東京医学社. 3 (2000)

Haruo Yamada、Naoto Miura、Takanari Aoki、Yoshinori Tanaka、Chotaka Yang、Masato Sakuma、Tsutomu Hara、Hironobu Miyai、Atsushi Fukatsu、Shinsei Futenma、Shinichi Kagami、Tetsuo Adachi、Yuichi Yamada：“肾脏和自由基 - 细胞外超氧化物歧化酶（EC） ) -SOD) 基因多态性 - 《东京工业大学. 3 (2000)》

山田晴生 他: "腎とフリーラジカル第5集-Extracellular Superoxide Dismutase(EC-SOD)遺伝子変異が血液透析患者の予後に及ぼす影響-"東京医学社. 3 (2001)

Haruo Yamada 等：“肾脏和自由基第 5 卷 - 细胞外超氧化物歧化酶 (EC-SOD) 基因突变对血液透析患者预后的影响”Tokyo Igakusha 3 (2001)。

Yamada H, Adachi T, Fukatsu A, Misao S, Yamada Y, Aoki T, Miura N, Sakumia M, Nishikawa K, Futeuma A, Kakumu S.: "Extracellular superoxide dismutase and glomerular mesangial cells : Its production and regulation"FEBS Letter. 519・22. 77-81 (2002)

Yamada H、Adachi T、Fukatsu A、Misao S、Yamada Y、Aoki T、Miura N、Sakumia M、Nishikawa K、Futeuma A、Kakumu S.：“细胞外超氧化物歧化酶和肾小球系膜细胞：其产生和调节”FEBS Letter 519・22。77-81（2002）

山田晴生 他: "医学のあゆみ 別冊 酸化ストレス"医歯薬出版株式会社. 4 (2001)

Haruo Yamada 等：《医学史特别版氧化应激》石药出版有限公司 4 (2001)