The pathogenesis of progressive chronic renal disease and therapeutic strategies, based on the axis of macrophages and myofibroblasts

基于巨噬细胞和肌成纤维细胞轴的进行性慢性肾病的发病机制和治疗策略

• 批准号: 22380173
• 负责人: YAMATE Jyoji
• 金额: $ 12.31万
• 依托单位: Osaka Prefecture University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22380173/
• 关键词: 腎線維化; マクロファージ; 筋線維芽細胞; 誘導因子; MHCクラスII; EMT; 尿細管再生; プロスタグランデン; 慢性腎臓病; 肝線維化; 皮膚創傷治癒線維化; 抗原提示マクロファージ; 細胞骨格; 胆管周囲線維化; 皮膚創傷治癒; Hsp25; カルポニン; 抗原提示能; 創傷治癒線維化; HSP25; Galactin-3

Fibrosis is developed after tissue injury. Regardless etiology,interstitial fibrosis occurs after renal injury, then leading to chronic kidney disease.The properties of macrophages and myofibroblasts, both which play central roles in fibrosis, were investigated using cisplatin-induced rat renal failure model. CD68 macrophages appeared at early stages, whereas at the advanced stages, MHC class II-expressing macrophages and lymphocytes appeared. Besides epithelial-mesenchymal transition (EMT), myofibroblasts may be derived from mesenchymal cells such as medullary interstitial cells and pericytes in lineage of stem cells. EMT phenomenon was seen exclusively in abnormally regenerating renal epithelia; the formation is inhibited by PGE2 but promoted by osteopontin. Characteristics of hepatic, pulomonary and cutaneous fibrosis were investigated as well. Clarifying the pathogenesis of fibrosis could lead to exploration of possible therapies.

组织损伤后发生纤维化。无论病因如何，肾损伤后都会发生间质纤维化，进而导致慢性肾脏疾病。利用顺铂诱导的大鼠肾衰竭模型研究了在纤维化中起核心作用的巨噬细胞和肌成纤维细胞的特性。 CD68巨噬细胞在早期出现，而在晚期则出现表达MHC II类的巨噬细胞和淋巴细胞。除了上皮间质转化（EMT）之外，肌成纤维细胞可能源自间充质细胞，例如干细胞谱系中的髓质间质细胞和周细胞。 EMT 现象仅见于异常再生的肾上皮细胞； PGE2 抑制该形成，但骨桥蛋白促进该形成。 还研究了肝脏、肺和皮肤纤维化的特征。阐明纤维化的发病机制可能会导致对可能的治疗方法的探索。

项目成果

Comparisons of properties of macrophages and myofibroblasts between two different cutaneous fibrosis rat models.Juniantito V

两种不同皮肤纤维化大鼠模型巨噬细胞和肌成纤维细胞特性比较Juniantito V

• 发表时间: 2011
• 作者: 井澤武史;矢野遼;桑村 充;山手丈至
• 通讯作者: 山手丈至

四塩化炭素誘発肝病変におけるHeat shock protein 25 とAdipophilin の発現動態

四氯化碳所致肝损伤中热休克蛋白25和Adipophilin的表达动态

• 发表时间: 2011
• 作者: 藤澤可恵;山本絵美;増野功一;土屋紀子,松 嶋周一;高須伸夫;井澤武史;桑村 充;鳥井幹則;山手丈至
• 通讯作者: 山手丈至

Alpha-naphthylisothiocyanate（ANIT）により誘発したラットの急性と慢性胆管病変におけるマクロファージと筋線維芽細胞の特性比較

α-萘基异硫氰酸酯（ANIT）所致大鼠急、慢性胆管病变中巨噬细胞和肌成纤维细胞特征的比较

• 作者: Golbar;et al.,
• 通讯作者: et al.,

Immunophenotypical properties of macrophages and myofibroblasts in fasciola-infested cirrhotic cattle liver

片形吸虫感染的肝硬化牛肝中巨噬细胞和肌成纤维细胞的免疫表型特性

• 发表时间: 2011
• 作者: Golbar HM,井澤武史;桑村 充;山手丈至
• 通讯作者: 山手丈至

シスプラチン誘発ラット腎障害モデルでの再生尿細管におけるβ-カテニンの発現

顺铂诱导大鼠肾损伤模型再生肾小管中β-catenin的表达

• 发表时间: 2012
• 作者: 寺田直美;市川智彩;井澤武史;桑村 充;山手丈至
• 通讯作者: 山手丈至