Site-specific expression of IQGAP1 in human nephrons
Site-specific expression of IQGAP1 in human nephrons
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DOI：
10.1007/s10735-019-09811-5
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发表时间：
2019-01
影响因子：
3.2
通讯作者：
Ping Wang;Xiaojie Gong;Peizhong Guan;Dong Ji;Linna Du;Dongmei Xu;Yipeng Liu
中科院分区：
文献类型：
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作者：
Ping Wang;Xiaojie Gong;Peizhong Guan;Dong Ji;Linna Du;Dongmei Xu;Yipeng Liu
IQGAP 1是一种多功能的190 kDa支架蛋白，在调节细胞粘附、迁移、增殖、分化、极化和细胞骨架重塑方面发挥着重要作用。IQGAP 1在人体器官中广泛表达，在肾脏中高度表达。目前，IQGAP 1在人肾单位中的位点特异性表达尚不清楚。我们采用Western blotting分析、免疫组化和免疫双标记共聚焦显微镜技术研究IQGAP 1在人肾单位中的表达和分布。我们发现IQGAP 1在人足细胞和肾小球内皮细胞中强表达，而在肾小球系膜细胞中弱表达。在人肾小管中，IQGAP 1在集合管中强表达，在近曲小管、髓袢、远曲小管和连接小管中中等表达。IQGAP 1在近曲小管顶膜、髓袢的粗降支和粗升支及集合管中表达较强。IQGAP 1主要表达于连接小管的基底外侧膜，在髓袢的细支和远曲小管中呈弥漫性表达。IQGAP 1与F-actin之间的相互作用表明，细胞骨架调节可能是IQGAP 1介导人肾单位效应的潜在机制。据我们所知，这是第一个报告的IQGAP 1在人类肾单位的特异性表达和差异亚细胞定位。IQGAP 1的位点特异性表达模式表明IQGAP 1可能在不同的人肾单位节段中发挥不同的作用。
IQGAP1 is a multifunctional, 190-kDa scaffolding protein that plays an important role in the regulation of cell adhesion, migration, proliferation, differentiation, polarization and cytoskeletal remodeling. IQGAP1 is ubiquitously expressed in human organs and is highly expressed in the kidney. Currently, the site-specific expression of IQGAP1 in the human nephrons is unclear. We performed Western blotting analysis, immunohistochemistry and double-immunolabeling confocal microscopic analysis of IQGAP1 with specific biomarkers of each nephron segment to study the expression and distribution of IQGAP1 in human nephrons. We found that IQGAP1 was strongly expressed in human podocytes and glomerular endothelial cells, but weakly expressed in glomerular mesangial cells. In human renal tubules, IQGAP1 was strongly expressed in the collecting duct, moderately expressed in the proximal tubule, medullary loop, distal convoluted tubule and connecting tubule. IQGAP1 staining was much stronger in the apical membrane in the proximal tubule, thick descending limb and thick ascending limb of medullary loop and collecting duct. However, the expression of IQGAP1 was mainly in the basolateral membrane of the connecting tubule, and diffusely in the thin limb of medullary loop and distal convoluted tubule. The interaction between IQGAP1 and F-actin suggested that cytoskeleton regulation may be the underlying mechanism mediating the effect of IQGAP1 in human nephrons. To the best of our knowledge, this is the first report of specific expression and differential subcellular location of IQGAP1 in human nephrons. The site-specific expression pattern of IQGAP1 suggests that IQGAP1 may play diverse roles in various human nephron segments.