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Melamine promotes calcium crystal formation in three-dimensional microfluidic device

机译:三聚氰胺促进三维微流控装置中钙晶体的形成

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摘要

Melamine, which induces proximal tubular (PT) cell damage has a greater nephrotoxic effect when combined with cyanuric and uric acids; however, it is unknown whether such effect can stimulate calcium phosphate (CaP)/calcium oxalate (CaOx) stone formation. Here, we show that melamine acts as an inducer of CaP, CaOx and CaP + CaOx (mixed) crystal formations in a time and concentration-dependent manner by stabilizing those crystals and further co-aggregating with melamine. To explore the physiological relevance of such melamine-augmented calcium crystal formation, we used 2-dimensional (2D) and 3D microfluidic (MF) device, embedded with PT cells, which also resembled the effect of melamine-stimulated CaP, CaOx and mixed crystal formation. Significantly, addition of preformed CaP and/or CaOx crystal in the presence of melamine, further potentiated those crystal formations in 3D MFs, which helped the growth and aggregation of mixed crystals. Our data show that the mechanism of such predisposition of stone formation could be largely due to co-crystallization between melamine and CaP/CaOx and pronounced effect on induction of stone-forming pathway activation in 3D MF. Taken together, melamine-induced CaP and/or CaOx crystal formation ex-vivo will help us in understanding the larger role of melamine as an environmental toxicant in producing the pathology in similar cellular microenvironments.
机译:当三聚氰胺与氰尿酸和尿酸联合使用时,会引起近端肾小管(PT)细胞损伤,具有更大的肾毒性作用。但是,尚不清楚这种作用是否能刺激磷酸钙(CaP)/草酸钙(CaOx)结石形成。在这里,我们表明三聚氰胺通过稳定那些晶体并与三聚氰胺进一步共聚集,以时间和浓度依赖的方式,充当CaP,CaOx和CaP ++ CaOx(混合)晶体形成的诱导剂。为了探索这种三聚氰胺增强的钙晶体形成的生理相关性,我们使用嵌入了PT细胞的二维(2D)和3D微流体(MF)装置,这也类似于三聚氰胺刺激的CaP,CaOx和混合晶体的作用编队。值得注意的是,在三聚氰胺的存在下添加预先形成的CaP和/或CaOx晶体,可以进一步增强3D MF中的晶体形成,从而有助于混合晶体的生长和聚集。我们的数据表明,这种易形成结石的机制可能主要归因于三聚氰胺与CaP / CaOx之间的共结晶以及对3D MF中诱导结石途径活化的显着影响。两者合计,三聚氰胺诱导的CaP和/或CaOx晶体体外形成将帮助我们理解三聚氰胺作为环境毒物在类似细胞微环境中产生病理学中的更大作用。

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