Proteomics of Crystal–Cell Interactions: A Model for Kidney Stone Research

Abstract

Nephrolithiasis/urolithiasis (i.e., kidney stone disease) remains a global public health problem with increasing incidence/prevalence. The most common chemical composition of kidney stones is calcium oxalate that initiates stone formation by crystallization, crystal growth, crystal aggregation, crystal–cell adhesion, and crystal invasion through extracellular matrix in renal interstitium. Among these processes, crystal–cell interactions (defined as “the phenomena in which the cell is altered by any means of effects from the crystal that adheres onto cellular surface or is internalized into the cell, accompanying with changes of the crystal, e.g., growth, adhesive capability, degradation, etc., induced by the cell”) are very important for crystal retention in the kidney. During the past 12 years, proteomics has been extensively applied to kidney stone research aiming for better understanding of the pathogenic mechanisms of kidney stone formation. This article provides an overview of the current knowledge in this field and summarizes the data obtained from all the studies that applied proteomics to the investigations of crystal–cell interactions that subsequently led to functional studies to address the significant impact or functional roles of the expression proteomics data in the pathogenesis of kidney stone disease.

Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals

“…After characterization by a stone component analyzer (LIIR-20, Lambda scientific, Tianjin China), the calcium oxalate kidney stone was fully crushed into powder by sterilized mortar and pestle and then prepared into COM suspension. Briefly, the crystals were suspended with serum-free DMEM at a final concentration of 100 μg/ mL (per volume of medium) [14,24], which was demonstrated not to cause severe cytotoxicity to renal tubular cells or increase percentage of cell death [24], but induce alterations in cellular proteome and reflect response of the renal epithelial cells to the COM crystals in vivo [18,24,25]. The kidney stone specimen was used in accordance with the hospital ethical review and the patient's informed consent.…”

“…Crystal-cell interaction model is widely used for kidney stone research for better understanding of the pathogenic mechanisms of kidney stone formation [18]. MDCK renal tubular cells (a cell line derived from dog kidney exhibiting distal renal tubule phenotype) and HK-2 cells (an immortalized human kidney proximal tubule epithelial cell line) are the most frequently used cells in crystal-cell interaction model [18].…”

“…Crystal-cell interaction model is widely used for kidney stone research for better understanding of the pathogenic mechanisms of kidney stone formation [18]. MDCK renal tubular cells (a cell line derived from dog kidney exhibiting distal renal tubule phenotype) and HK-2 cells (an immortalized human kidney proximal tubule epithelial cell line) are the most frequently used cells in crystal-cell interaction model [18]. Although several previous studies have found some new candidate proteins, further studies are necessary, since the COMcrystals prepared by calcium chloride dihydrate and sodium oxalate are different from the clinical COM-stone samples and use of cells from different species of the nephron may result in different findings.…”

Specific populations of urinary extracellular vesicles and proteins differentiate type 1 primary hyperoxaluria patients without and with nephrocalcinosis or kidney stones

“…Although many proteins have been implicated in crystal-renal cell interactions and KS pathogenesis [60][61][62], the exact group of proteins ultimately involved in soft tissue calcification are not completely known. At a minimum, the differential expression of urinary proteins in PH1 patients with NC compared to PH1 patients without NC or KS and with KS suggests NC is different from stone pathogenesis.…”

miR-155-5p Promotes Oxalate- and Calcium-Induced Kidney Oxidative Stress Injury by Suppressing MGP Expression

“…Another study found that ROS regulate different nuclear factors such as NF-κB, AP-1, and different genes c-myc and cjun [21]. Activation of these signaling pathways results in changes in the expression of many stone-related proteins, which promote or inhibit stone formation [33,34]. From the literature, we found that oxidative stress injury might play crucial roles in the pathogenesis of CaOx.…”