Glomerular and renal vascular structural changes in α8 integrin-deficient mice
Glomerular and renal vascular structural changes in α8 integrin-deficient mice
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DOI：
10.1097/01.asn.0000082999.46030.fe
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发表时间：
2003-09-01
影响因子：
13.6
通讯作者：
Hartner, A
中科院分区：
文献类型：
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作者：
Haas, CS;Amann, K;Hartner, A
整合素是在发育和成人组织中调节细胞-基质相互作用的基质受体。在成人肾脏中，alpha8链在肾小球系膜细胞和血管平滑肌细胞中特异性表达。alpha8缺陷（alpha8-/-）小鼠表现出肾脏体积的减少，其范围可以从肾脏完全发育不全到肾脏的发育仅比野生型肾脏略小。这些肾脏未见组织学异常。然而，考虑到a8在肾小球和肾血管中的显著表达，alpha8-/-小鼠的肾脏似乎不太可能完全正常。因此，研究了成年alpha8-/-小鼠的肾脏表型，以评估肾脏组织中更细微的形态学改变。与野生型对照动物相比，Alpha8 -/-小鼠表现出肾单位数量的显著减少和肾小球体积的显著增加。野生型和α 8-/-小鼠蛋白尿无显著差异。定量形态学分析显示，与野生型小鼠相比，α 8-/-小鼠肾小球呈高细胞性，系膜细胞数量增加。与野生型小鼠相比，α 8-/-小鼠系膜基质沉积（如胶原IV和α 8配体纤维连接蛋白）增加。在α 8-/-小鼠的肾小球中检测到通常不存在于肾小球中的胶原I和III。其他肾小球整合素染色显示，在α 8-/-小鼠中，胶原受体α 2整合素的丰度增加。α 8-/-小鼠肾小球毛细血管长度密度显著高于野生型小鼠。α 8-/小鼠的皮质动脉血管壁没有改变，但小管周围网络的毛细血管变宽。尽管alpha8在系膜和血管中表达强烈，但在alpha8-/-小鼠中肾小球和肾血管的改变相对较轻。与对照动物相比，只有年老的alpha8-/-小鼠表现出肾小球毛细血管增宽。结果表明，至少在年轻的alpha8-/-小鼠中，缺乏alpha8可以在很大程度上得到补偿。现在还不是。明确在alpha8-/-小鼠中，肾小球中不正常存在的胶原的出现以及胶原受体alpha2丰度的增加是否有助于维持肾小球结构。所涉及的补偿机制将是未来研究的主题。
Integrins are matrix receptors that regulate cell-matrix interactions during development and in adult tissue. In the adult kidney, the alpha8 chain is specifically expressed in glomerular mesangial cells and vascular smooth muscle cells. alpha8-deficient (alpha8-/-) mice demonstrate reductions in renal mass, which can range from complete renal agenesis to the development of kidneys that are only slightly smaller than wild-type kidneys. No histologic abnormalities of these kidneys have been described. However, considering the prominent expression of a8 in glomeruli and renal vessels, it seemed unlikely that the kidneys of alpha8-/- mice would be completely normal. Therefore, the renal phenotype of adult alpha8-/- mice was investigated, for assessment of more subtle morphologic alterations in kidney tissue. alpha8-/- mice displayed a significant reduction in nephron number and an increase in glomerular volume, compared with wild-type control animals. Albuminuria was not different in wild-type and alpha8-/- mice. Quantitative morphologic analyses revealed that the glomeruli of alpha8-/- mice were hypercellular, with an increased number of mesangial cells, compared with wild-type mice. Mesangial matrix deposition (as demonstrated for collagen IV and the alpha8 ligand fibronectin) was expanded in alpha8-/- mice, compared with wild-type mice. Collagens I and III, which are not normally present in glomeruli, were detected in the glomeruli of alpha8-/- mice. Staining for other glomerular integrins demonstrated an increased abundance of the collagen receptor alpha2 integrin in alpha8-/- mice. The glomerular capillary length density was significantly greater in alpha8-/- mice than in wild-type mice. Cortical arterial vessel walls were not altered in alpha8-/mice, but the capillaries of the peritubular network were widened. Despite the strong mesangial and vascular expression of alpha8, glomerular and renal vascular alterations in alpha8-/- mice were relatively mild. Only aged alpha8-/- mice demonstrated increased glomerular capillary widening, compared with control animals. The results suggest that the lack of alpha8 can be largely compensated for, at least in younger alpha8-/- mice. It is not yet. clear whether the occurrence of collagens that are not normally present in glomeruli and the increased abundance of the collagen receptor alpha2 contribute to maintaining the glomerular structure in alpha8-/- mice. The compensatory mechanisms involved will be the subject of future research.