The initial and subsequent inflammatory events during calcium oxalate lithiasis.
The initial and subsequent inflammatory events during calcium oxalate lithiasis.
复制标题
DOI：
10.1016/j.cca.2010.03.015
复制
发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
J. Yuen;M. Gohel;N. Poon;D. Shum;P. Tam;D. Au
中科院分区：
文献类型：
--
作者：
J. Yuen;M. Gohel;N. Poon;D. Shum;P. Tam;D. Au
结晶被认为是尿石症的起始步骤，尽管尚不清楚肾元内第一个结晶成核发生的位置。方法采用完整的人近端HK-2细胞单层双室培养系统，检测草酸钙的直接成核及其后续事件，包括晶体保留、细胞损伤、内吞作用和透明质酸（HA）的表达。结果在高钙血症和高血氧血症条件下，二水合草酸钙（COD）成核并结合在HK-2细胞的顶端表面。电镜显示，这些细胞在暴露于cod后的18h内表现出轻微的细胞损伤，并内化了一些粘附的晶体。在完全培养液中长时间孵育造成严重损害，破坏了单层的完整性。此外，在收获的培养基中检测到透明质酸二糖，并与哈斯-3 mRNA表达相关。结论人近端细胞能够内化COD晶体，并直接成核到细胞顶表面，从而引发细胞损伤和ha -3特异性透明质酸合成，作为炎症反应。近端小管细胞通过内吞作用在促进尿石症中发挥重要作用，并创造炎症环境，由此管状液中的游离透明质酸可以在远端小管和集合小管的后段充当晶体结合分子。
BACKGROUNDCrystallization is believed to be the initiation step of urolithiasis, even though it is unknown where inside the nephron the first crystal nucleation occurs.METHODSDirect nucleation of calcium oxalate and subsequent events including crystal retention, cellular damage, endocytosis, and hyaluronan (HA) expression, were tested in a two-compartment culture system with intact human proximal tubular HK-2 cell monolayer.RESULTSCalcium oxalate dihydrate (COD) was nucleated and bound onto the apical surface of the HK-2 cells under hypercalciuric and hyperoxaluric conditions. These cells displayed mild cellular damage and internalized some of the adhered crystals within 18h post-COD-exposure, as revealed by electron microscopy. Prolonged incubation in complete medium caused significant damage to disrupt the monolayer integrity. Furthermore, hyaluronan disaccharides were detected in the harvested media, and were associated with HAS-3 mRNA expression.CONCLUSIONHuman proximal cells were able to internalize COD crystals which nucleated directly onto the apical surface, subsequently triggering cellular damage and HAS-3 specific hyaluronan synthesis as an inflammatory response. The proximal tubule cells here demonstrate that it plays an important role in facilitating urolithiasis via endocytosis and creating an inflammatory environment whereby free hyaluronan in tubular fluid can act as crystal-binding molecule at the later segments of distal and collecting tubules.