Females have less incidence/prevalence of kidney stone disease than males. Estrogen thus may serve as the protective factor but with unclear mechanism. This study explored cellular mechanism underlying such stone preventive mechanism of estrogen. MDCK renal tubular cells were incubated with or without 20 nM 17β-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 and 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 caused 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.

Proteomics. 2019 Sep 01 [Epub ahead of print]

Paleerath Peerapen, Visith Thongboonkerd

Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.