Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation

This study explored cellular mechanism underlying such stone preventive mechanism of estrogen. MDCK renal tubular cells were incubated with or without 20 nM 17 β‐estradiol for 7 days. Comparative proteomics revealed 58 differentially expressed proteins in estrogen‐treated vs. control cells that were successfully identified by nanoLC‐ESI‐Q‐TOF MS/MS. Interestingly, these altered proteins were involved mainly in “binding and receptor”, “metabolic process”, and “migration and healing” networks. Functional investigations demonstrated reduction of calcium oxalate (CaOx) crystal‐binding capability of the estrogen‐treated cells consistent with the decreased levels of annexin A1 and α‐enolase (the known CaOx crystal‐binding receptors) on the cell surface. High‐calcium a nd high‐oxalate challenge initially enhanced surface expression of annexin A1 and α‐enolase, respectively, both of which returned to their basal levels by estrogen. Additionally, estrogen reduced intracellular ATP level and promoted cell migration and tissue healing. Taken together, estrogen ca used changes in cellular proteome of renal tubular cells that led to decreased surface expression of CaOx crystal receptors, reduced intracellular metabolism, and enhanced cell proliferation and tissue healing, all of which might contribute, at least in part, to stone prevention.This article is protected by copyright. All rights reserved
Source: Proteomics - Category: Biochemistry Authors: Tags: Research Article Source Type: research