Glomerular Repair Retardation via Blocking of Angiotensin II Type 1a Receptor Pathway in a Mouse Glomerulonephritis Model
Glomerular Repair Retardation via Blocking of Angiotensin II Type 1a Receptor Pathway in a Mouse Glomerulonephritis Model
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DOI：
10.1159/000346954
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Kohno, Shigeru
中科院分区：
文献类型：
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作者：
Hayashi, Waka;Obata, Yoko;Kohno, Shigeru
背景/目的：为了研究血管紧张素 II (ATII) 1a 型受体 (AT1-R) 通路在肾组织损伤和修复中的作用，我们使用 AT1-R 缺陷 (AT1a-/-) 小鼠和 AT1-R 拮抗剂治疗的小鼠，研究了哈布蛇毒 (HSV) 诱导的肾小球肾炎小鼠模型中的可逆性肾小球损伤。方法：通过对 AT1a+/+ 小鼠（HSV 组）、AT1a-/- 小鼠（KO-HSV 组）和 AT1-R 拮抗剂治疗的 BL6 小鼠（HSV-ARB 组）单次注射 HSV 诱导实验性肾小球肾炎。分析 IV 型胶原、CD31 和血管内皮生长因子 (VEGF) 的形态变化和表达水平。结果：HSV 组在第 7 天显示系膜基质扩张增加，到第 56 天恢复到注射前水平，而 KO-HSV 组在第 7 天至第 56 天观察到系膜基质扩张和 IV 型胶原表达增加。与HSV组相比，KO-HSV组显示出更少的CD31阳性毛细血管袢，并且肾小球中的VEGF阳性细胞数量显着减少。 KO-HSV 组给予 VEGF 促进肾小球毛细血管修复和重建。 HSV-ARB 组表现出与 KO-HSV 组相同的肾小球修复延迟。结论：我们的结果表明，阻断 ATII-AT1R 通路可通过抑制血管生成延迟肾小球修复，进而减少 VEGF 的诱导。版权所有 (C) 2013 S. Karger AG，巴塞尔
Background/Aims: To examine the role of the angiotensin II (ATII) type 1a receptor (AT1-R) pathway in renal tissue damage and repair, we investigated reversible glomerular injury in a mouse model of habu snake venom (HSV)-induced glomerulonephritis using AT1-R-deficient (AT1a-/-) mice and AT1-R antagonist-treated mice. Methods: Experimental glomerulonephritis was induced by single administration of HSV to AT1a+/+ mice (HSV group) and AT1a-/- mice (KO-HSV group) and AT1-R antagonist-treated BL6 mice (HSV-ARB group). Morphological change and expression levels of type IV collagen, CD31, and vascular endothelial growth factor (VEGF) were analyzed. Results: The HSV group showed increased mesangial matrix expansion on day 7, which returned to preinjection levels by day 56, while mesangial matrix expansion and increased type IV collagen expression were seen throughout days 7 to 56 in the KO-HSV group. The KO-HSV group showed fewer CD31-positive capillary loops and a marked decrease in the number of VEGF-positive cells in the glomeruli than the HSV group. VEGF administration to the KO-HSV group facilitated glomerular capillary repair and reconstruction. The HSV-ARB group showed the same delay in glomerular repair as that seen in the KO-HSV group. Conclusion: Our results indicate that blocking of the ATII-AT1R pathway delays glomerular repair via angiogenesis inhibition, followed by reduced induction of VEGF. Copyright (C) 2013 S. Karger AG, Basel