Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.
OBJECTIVE
Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury.


METHODS
The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis.


RESULTS
Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury.


CONCLUSIONS
The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease.
Amity Institute of Biotechnology (AIB), Amity University Uttar Pradesh, Noida, Uttar Pradesh, India.
Shifa
S
Narula
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida, Uttar Pradesh, India.
Simran
S
Tandon
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, Punjab, India.
Shrawan Kumar
SK
Singh
Amity Institute of Biotechnology (AIB), Amity University Uttar Pradesh, Noida, Uttar Pradesh, India. Electronic address: ctandon@amity.edu.
Chanderdeep
C
Tandon
D000818:Animals; D002129:Calcium Oxalate / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D061985:Madin Darby Canine Kidney Cells / Q000187:drug effects / Q000648:ultrastructure
D016326:Extracellular Matrix Proteins; D002129:Calcium Oxalate
Calcium oxalate monohydrate (COM); Kidney stones; Matrix proteins; Modulators; Nephrolithiasis