Characterization of hyaluronan cable structure and function in renal proximal tubular epithelial cells
Characterization of hyaluronan cable structure and function in renal proximal tubular epithelial cells
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DOI：
10.1038/sj.ki.5001760
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发表时间：
2006-10-01
影响因子：
19.6
通讯作者：
Phillips, A. O.
中科院分区：
文献类型：
--
作者：
Selbi, W.;de la Motte, Ca;Phillips, A. O.
糖胺聚糖透明质酸（HA）的改变已在许多肾脏疾病中得到证实。我们已经证明，肾近端肾小管上皮细胞（PTC）包围自己在一个有组织的细胞周基质或“外套”，这是与细胞迁移，也形成细胞周HA电缆样结构，调节PTC单核白细胞的相互作用与HA在体外。本研究的目的是表征PTC-HA组装成细胞周围电缆的潜在调控机制。HA电缆由PTC在不存在血清的情况下产生。免疫组织化学分析表明，HA电缆的蛋白质和多功能蛋白聚糖的相互间α-抑制剂（I α I）家族的成分的掺入。添加针对I α I/P α I的抗体（前α抑制剂）抑制缆线形成。相反，抑制肿瘤坏死因子-α-刺激基因6（TSG-6）对电缆形成没有影响，表明它们的产生与TSG-6已知的重链转移活性无关。HAS 3的过表达与HA电缆形成的诱导相关，并且还增加了HA掺入细胞周涂层中。在功能上，这分别导致增强的HA依赖性单核细胞结合和细胞迁移。在HAS 3过表达细胞中，CD 44和胰蛋白酶释放的细胞相关HA的细胞表面表达增加。此外，透明质酸酶（hyal 1和hyal 2）和bikunin mRNA表达增加，而P α I HC 3 mRNA表达在转染细胞中无变化。这些数据证明了Ifos/派在电缆形成中的重要性，并表明HAS 3的表达可能对HA电缆组装至关重要。
Alteration in the glycosaminoglycan hyaluronan (HA) has been demonstrated in numerous renal diseases. We have demonstrated that renal proximal tubular epithelial cells (PTCs) surround themselves in vitro with HA in an organized pericellular matrix or 'coat', which is associated with cell migration, and also form pericellular HA cable-like structures which modulate PTC-mononuclear leukocytes interactions. The aim of this study was to characterize potential regulatory mechanism in the assembly of PTC- HA into pericellular cables. HA cables are generated by PTCs in the absence of serum. Immunohistochemical analysis demonstrates the incorporation of components of the inter-alpha-inhibitor (I alpha I) family of proteins and versican into HA cables. Addition of an antibody to I alpha I/P alpha I (pre-alpha-inhibitor) inhibits cable formation. In contrast, inhibition of tumor necrosis factor-a-stimulated gene 6 (TSG-6) has no effect on cable formation, suggesting that their generation is independent of the known heavy-chain transfer activity of TSG-6. Overexpression of HAS3 is associated with induction of HA cable formation, and also increased incorporation of HA into pericellular coats. Functionally, this resulted in enhanced HA-dependent monocyte binding and cell migration, respectively. Cell surface expression of CD44 and trypsin-released cell-associated HA were increased in HAS3-overexpressing cells. In addition, hyaluronidase (hyal1 and hyal2) and bikunin mRNA expression were increased, whereas P alpha I HC3 mRNA expression was unchanged in the transfected cells. The data demonstrate the importance of IaI/PaI in cable formation and suggest that expression of HAS3 may be critical for HA cable assembly.