Molecular mechanism of spontaneous remission from renal injury

肾损伤自发缓解的分子机制

• 批准号: 13671118
• 负责人: MIYAZAKI Masanobu
• 金额: $ 2.37万
• 依托单位: Nagasaki University
• 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 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671118/
• 关键词: angiotensin II; aldosterone; angiogenesis; glomerulonephritis; VEGF; CYP11B2; HSP47; Ets-1; 腎炎; 再生; マトリックスメタロプロテナーゼ; 骨髄細胞

In the present study, we examined the role of angiotensin II in the process of spontaneous remission of glomerular injury in experimental mesangial proliferative glomerulonephritis and tested the expression of mRNA for CYP11B, the key enzyme of aldosterone synthesis in human renal biopsy specimens using in situ hybridization. We induced reversal mesangial proliferative glomerulonephritis by Habu-snake venom injection. Compared with wild type mice, the delay of remission from glomerular injury, including expansion of mesangial area and reduced number of glomerular capillary wall, was observed in mice without angiotensin II receptor type 1. Treatment of VEGF (vascular endothelial cell growth factor) promoted restoration of glomerularr injury in the model. In the second study, CYP11B2 mRNA was expressed in glomerular cells, such as mesangial cells, glomerular epithelial and endothelial cells, and infiltrating cells and atrophic tubular cells in the interstitium. Moreover, these expressions of CYP 11 B2 mRNA were significantly correlated with the degree of their tissue injury. Our results suggested that angiotensin II is important in the reconstitution of glomerular capillary and that aldosterone produced in human renal tissue was involved in renal tissue damage.

本研究旨在探讨血管紧张素II在系膜增生性肾炎肾小球损伤自发缓解过程中的作用，并用原位杂交技术检测肾活检组织中醛固酮合成关键酶--细胞色素P11B基因的表达。用哈布蛇毒注射诱导大鼠肾小球系膜增生性肾炎。与野生型小鼠相比，血管紧张素Ⅱ1型受体缺失的小鼠肾小球损伤缓解时间延迟，系膜面积扩大，肾小球毛细血管壁数减少。血管内皮细胞生长因子治疗可促进肾小球损伤的修复。在第二项研究中，肾小球系膜细胞、肾小球上皮细胞、肾小球内皮细胞、间质中的浸润性细胞和萎缩的肾小管上皮细胞等均有细胞色素P11B2的表达。此外，CYP 11B2mRNA的表达与其组织损伤程度显著相关。提示血管紧张素II在肾小球毛细血管重建中起重要作用，人肾组织产生的醛固酮参与了肾组织损伤。

项目成果

Mishima Y, Miyazkai M, Abe K, et al.: "Enhanced expression of heat shock protein 47 in rat model of peritoneal fibrosis."Perit Dial Int. 23(1). 14-22 (2003)

Mishima Y、Miyazkai M、Abe K 等人：“腹膜纤维化大鼠模型中热休克蛋白 47 的表达增强。”Perit Dial Int。

Nishino T, Miyazkai M, Abe K, et al.: "Antisense oligonucleotides against collagen-binding stress protein HSP 47 suppress peritoneal fibrosis in rats"Kidney Int. 64(3). 887-896 (2003)

Nishino T、Miyazkai M、Abe K 等人：“针对胶原蛋白结合应激蛋白 HSP 47 的反义寡核苷酸可抑制大鼠腹膜纤维化”Kidney Int。

Mishima Y, Miyazkai M, Abe K, et al.: "Enhanced expression of heat shock protein 47 in rat model of peritoneal fibrosis."Pent Dial Int. 23(1). 14-22 (2003)

Mishima Y、Miyazkai M、Abe K 等人：“腹膜纤维化大鼠模型中热休克蛋白 47 的表达增强。”Pent Dial Int。

Miyazaki M: "Regulation of renal extracellular matrix metabolism"Contrib Nephrol. (印刷中).

Miyazaki M：“肾细胞外基质代谢的调节”Contrib Nephrol（出版中）。

Ashizawa M.Miyazaki M, Abe K, et al.: "Detection of nuclear factor-kB in IgA nephropathy using Southwestern histocheroistry."Am J Kid Dis. 42(1). 76-86 (2003)

Ashizawa M.Miyazaki M、Abe K 等人：“使用西南组织化学法检测 IgA 肾病中的核因子-kB。”Am J Kid Dis。