Study of proper mechanism of repair and regeneration after kidney injury evoked by novel gammalactone low molecular compounds derivatives with cytokines

新型γ内酯低分子化合物衍生物与细胞因子诱导肾损伤修复与再生的适当机制研究

• 批准号: 21592083
• 负责人: ISHIBASHI Michio
• 金额: $ 2.91万
• 依托单位: Nara 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: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592083/
• 关键词: 一側腎尿管閉塞解除ラットモデル; ガンマラクトン低分子化合物; ベンゾイソフラノン低分子化合物; TNF-α; アポトーシス; ガレクチン-3; マトリックス応答; 血管新生; 1型コラーゲン; CD98/4F2hc/rBAT; ガンマラクトン化合物; ベンゾイソフラノン化合物; リコンビナントTNF-alpha; 抗アポトーシス活性; 急性腎障害修復と再生; マクロファージ; rBAT heavy chain of heterodimeric aminoacid tran

Using animal model of unilateral ureteral, complete obstruction for 14 days with for six days observation after release, cellular infiltration and accumulation surrounding crossing points of bundle of descending varsa recta at the base of papillae, and propagating beneath depressed pelvic urothelial layer, was remarkably observed. Those pathologic lesions of tissue responses were tentatively called as "niches" for repair or regeneration of injured tubules. To explore"niches", beneficial treatment with recombinant rat TNF-alpha induced some proper matrix response with dominant type-1 collagen surrounding peritubular space. In contrast, treatment with novel benzoisofuranone induced another proper matrix response at "niches" with galectin-3 or rBAT positive cellular accumulation with angiogenesis and anti-apoptosis. The present studies suggested that ten times more potent benzoisofuranone compounds might be a candidate as promising medicine for intractable chronic renal allograft nephropathy

采用单侧输尿管动物模型，完全梗阻14 d，释放后观察6 d，观察到细胞在乳头基部直缩缩束交叉点周围的浸润和积聚，并在凹陷的盆腔尿路上皮层下繁殖。这些病理病变的组织反应被暂时称为“壁龛”修复或再生损伤小管。为了探索“壁龛”，用重组大鼠tnf - α进行有益治疗，诱导了一些适当的基质反应，主要是在管周间隙周围形成1型胶原。相比之下，新型苯并异呋喃酮治疗在“壁龛”诱导了另一种适当的基质反应，伴有半凝集素-3或rBAT阳性的血管生成和抗凋亡细胞积累。目前的研究表明，十倍强效的苯并异呋喃酮化合物可能是治疗顽固性慢性肾移植肾病的有希望的候选药物

项目成果

Important Repair/protective Process of Papillae in Renal Function and Morphology demonstrated by Use of 14 days-UUO-released Model and Small Synthetic Compounds in Rats

通过在大鼠体内使用 14 天 UUO 释放模型和小合成化合物证明乳头在肾功能和形态学中的重要修复/保护过程

• 发表时间: 2011
• 作者: M Ishibashi;T Nakatani;M Iwano;K Fujimoto;Y Kanai;Yoshihiko Hirao
• 通讯作者: Yoshihiko Hirao

Attenuation of UUO-induced renal injury treated with small molecule gammalactone inhibiting epithelial-mesenchymal transition as well as inducing cluster of rBAT-and E-cadherin-positive cells in renal papilla

小分子γ内酯治疗可减轻UUO引起的肾损伤，抑制上皮-间质转化并诱导肾乳头中rBAT和E-钙粘蛋白阳性细胞簇

• 发表时间: 2010
• 作者: M Ishibasi;M Iwano;K Fujimoto;Y Ito;Y Hirao;Y Kanai
• 通讯作者: Y Kanai

新規ベンゾイソフラノン誘導体による臓器組織の修復再生治療薬

使用新型苯并异呋喃酮衍生物进行器官组织修复和再生治疗

• 发表时间: 2011

Potentialisation of repair of renal tubular lesions by combined use of novel gammalactone derivatives and tumor necrosis factors

新型γ内酯衍生物和肿瘤坏死因子联合使用修复肾小管病变的潜力

• 发表时间: 2009
• 作者: M Ishibashi;M Iwano;K Fujimoto;Y Ito;Y Hirao;Y Kanai
• 通讯作者: Y Kanai