Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Proteomics. 2019 Oct;19(19):e1900095. doi: 10.1002/pmic.201900095. Epub 2019 Sep 18.
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 nm 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.
女性肾结石病的发病率/患病率低于男性。雌激素可能因此起到保护作用，但具体机制尚不清楚。本研究旨在探讨雌激素这种结石预防机制的细胞机制。将 Madin darby 犬肾 (MDCK) 肾小管细胞用或不用 20nm 17β-雌二醇孵育 7 天。比较蛋白质组学揭示了雌激素处理组与对照组细胞之间有 58 种差异表达蛋白，这些蛋白通过 nanoLC-ESI-Q-TOF-MS/MS 成功鉴定。有趣的是，这些改变的蛋白主要参与“结合和受体”、“代谢过程”和“迁移和愈合”网络。功能研究表明，雌激素处理细胞的钙草酸 (CaOx) 晶体结合能力降低，与细胞表面 annexin A1 和α-烯醇酶（已知的 CaOx 晶体结合受体）的水平降低一致。高钙和高草酸的最初挑战分别增强了 annexin A1 和α-烯醇酶的表面表达，而雌激素使它们均恢复到基础水平。此外，雌激素降低细胞内 ATP 水平，促进细胞迁移和组织愈合。总之，雌激素导致肾小管细胞的细胞蛋白质组发生变化，导致 CaOx 晶体受体的表面表达减少、细胞内代谢减少以及细胞增殖和组织愈合增强，这些都可能至少部分有助于结石预防。
