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.

在本研究中，我们检查了血管紧张素II在实验性肾小球增殖性肾小球肾炎中自发缓解肾小球损伤的作用，并测试了CYP11B的mRNA表达，CYP11b（CYP11B）是人肾脏活检在人肾脏活检中的关键酶（醛固酮合成）的关键酶。我们通过HABU-SNAKE毒液注射引起逆转肾小球肾小球肾炎。与野生型小鼠相比，在没有血管紧张素II受体II型1型的小鼠中观察到肾小球损伤的缓解延迟，包括肾小球区域的扩展和减少肾小球毛细血管壁的数量。处理模型中glomerarular损伤的VEGF（血管内皮细胞生长因子）的治疗。在第二项研究中，CYP11B2 mRNA在肾小球细胞中表达，例如肾小球细胞，肾小球上皮和内皮细胞，以及浸润的细胞和萎缩性管状细胞。此外，这些CYP 11 B2 mRNA的表达与其组织损伤程度显着相关。我们的结果表明，血管紧张素II在重建肾小球毛细血管中很重要，并且在人肾脏组织中产生的醛固酮参与肾脏组织损伤。

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。

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。

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。

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）。

Abe K: "Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization"Kidney Int. 60(1). 137-146 (2001)

Abe K：“通过原位杂交评估人类患病肾脏中补体 C5a 受体 mRNA 的增强表达”Kidney Int。