Département de Pharmacologie, Université de Sherbrooke, Sherbrooke, QC, J1H-5N4, Canada.
J Mol Recognit. 2011 Jul-Aug;24(4):733-40. doi: 10.1002/jmr.1110.
Interaction between hyaluronic acid (HA) present at the surface of tubular epithelial cells and calcium oxalate monohydrate (COM) crystals is thought to play an important role in kidney stone formation. AFM-based force spectroscopy, where HA is covalently attached to AFM-probes, was used to quantify the interaction between HA and the surfaces of COM crystals. The work of adhesion of the HA-probe as well as the rupture force of single HA molecules were quantified in order to understand the molecular regulation of HA binding to COM crystals. Our results reveal that HA adsorbs to the crystal surface in physiological conditions. We also observed increased adhesion when the pH is lowered to a value that increases the risk of kidney stone formation. HA adhesion to the COM crystal surface can be suppressed by citrate, a physiological inhibitor of stone retention currently used in the treatment and prevention of kidney stone formation. Interestingly, we also observed preferential binding of HA onto the [100] face versus the [010] face, suggesting a major contribution of the [100] faces in the crystal retention process at the surface of tubular epithelial cells and the promotion of stone formation. Our results clearly establish a direct role for the glycosaminoglycan HA present at the surface of kidney tubular epithelium in the process of COM crystal retention.
认为存在于管状上皮细胞表面的透明质酸（HA）与一水合草酸钙（COM）晶体之间的相互作用在肾结石形成中起着重要作用。基于原子力显微镜的力谱学，其中 HA 共价连接到 AFM 探针，用于定量 HA 与 COM 晶体表面之间的相互作用。为了了解 HA 与 COM 晶体结合的分子调控，量化了 HA 探针的粘附功以及单个 HA 分子的断裂力。我们的结果表明，HA 在生理条件下吸附在晶体表面上。当 pH 值降低到增加肾结石形成风险的值时，我们还观察到粘附力增加。柠檬酸是一种生理抑制剂，可抑制 HA 对 COM 晶体表面的粘附，目前用于肾结石形成的治疗和预防。有趣的是，我们还观察到 HA 优先结合到[100]面而不是[010]面，这表明[100]面在管状上皮细胞表面的晶体保留过程中以及结石形成过程中起主要作用。我们的结果清楚地确立了存在于肾脏管状上皮表面的糖胺聚糖 HA 在 COM 晶体保留过程中起直接作用。
