Abstract
The pathogenesis of kidney stone formation includes multi-step processes involving complex interactions between mineral components and protein matrix. Calcium-binding proteins in kidney stones have great influences on the stone formation. The spatial distributions of these proteins in kidney stones are essential for evaluating the in vivo effects of proteins on the stone formation, although the actual distribution of these proteins is still unclear. We reveal micro-scale distributions of three different proteins, namely osteopontin (OPN), renal prothrombin fragment 1 (RPTF-1), and calgranulin A (Cal-A), in human kidney stones retaining original mineral phases and textures: calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD). OPN and RPTF-1 were distributed inside of both COM and COD crystals, whereas Cal-A was distributed outside of crystals. OPN and RPTF-1 showed homogeneous distributions in COM crystals with mosaic texture, and periodically distributions parallel to specific crystal faces in COD crystals. The unique distributions of these proteins enable us to interpret the different in vivo effects of each protein on CaOx crystal growth based on their physico-chemical properties and the complex physical environment changes of each protein. This method will further allow us to elucidate in vivo effects of different proteins on kidney stone formation.
Highlights
The pathogenesis of kidney stone formation includes multi-step processes involving complex interactions between mineral components and protein matrix
We investigated the distribution of three different proteins, osteopontin (OPN), renal prothrombin fragment 1 (RPTF-1), and calgranulin A (Cal-A), in thin sections of calcium oxalate (CaOx) stones
Based on microscopic observation coupled with FT-infrared spectroscopy (IR) analysis, domains of the kidney stone samples were categorized into three types of textures that are consistent with that reported in Schubert and B rien[23]: irregular texture composed of euhedral calcium oxalate dihydrate (COD) crystals (Type 1, referred to as euhedral COD aggregate; Fig. 1c), mosaic texture composed of irregular oriented calcium oxalate monohydrate (COM) crystals (Type 2, referred to as mosaic COM; Fig. 1f), and concentrically laminated COM crystals (Type 3, referred to as concentric COM; Fig. 1i)
Summary
The pathogenesis of kidney stone formation includes multi-step processes involving complex interactions between mineral components and protein matrix. In the real stone formation environments, numbers of proteins work simultaneously, and the urine composition in the concentrations of proteins, calcium ion, and oxalate fluctuates This concern motivated us to investigate real human kidney stones to find the real effects of proteins on crystal growth. Protein identification in kidney stones has been conducted with sliced sections of kidney stones in which CaOx crystals are completely removed by d ecalcification[20,21] This approach is useful for finding the distribution of a protein in kidney stones that potentially helps to understand specific protein effects on stone formation. The importance of mineral information of kidney stones that can be acquired by the identifications of crystal phases and the crystal texture classifications conducted using slice sections and polished thin sections of kidney stones with optical microscopy has been shown by more than 70 years of previous studies[22,23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
