Premium
Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation
Author(s) -
Peerapen Paleerath,
Thongboonkerd Visith
Publication year - 2019
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201900095
Subject(s) - estrogen , estrogen receptor , annexin a1 , annexin a2 , annexin , kidney stone disease , kidney , microbiology and biotechnology , estrogen receptor alpha , estrogen receptor beta , receptor , proteomics , biology , medicine , endocrinology , kidney stones , cell , biochemistry , breast cancer , gene , cancer
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 explores cellular mechanism underlying such stone preventive mechanism of estrogen. Madin darby canine kidney (MDCK) renal tubular cells are incubated with or without 20 n m 17β‐estradiol for 7 days. Comparative proteomics reveals 58 differentially expressed proteins in estrogen‐treated versus control cells that are successfully identified by nanoLC–ESI–Q‐TOF‐MS/MS. Interestingly, these altered proteins are involved mainly in “binding and receptor,” “metabolic process,” and “migration and healing” networks. Functional investigations demonstrate 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 enhances surface expression of annexin A1 and α‐enolase, respectively, both of which return to their basal levels by estrogen. Additionally, estrogen reduces intracellular ATP level and promotes cell migration and tissue healing. Taken together, estrogen causes changes in cellular proteome of renal tubular cells that lead to decreased surface expression of CaOx crystal receptors, reduced intracellular metabolism, and enhanced cell proliferation and tissue healing, all of which may contribute, at least in part, to stone prevention.