Endoplasmic Reticulum Calcium Homeostasis in Kidney Disease: Pathogenesis and Therapeutic Targets

肾脏疾病中内质网钙稳态:发病机制和治疗靶点

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Abstract

Calcium (Ca(2+)) homeostasis is a crucial determinant of cellular function and survival. Endoplasmic reticulum (ER) acts as the largest intracellular Ca(2+) store that maintains Ca(2+) homeostasis through the ER Ca(2+) uptake pump, sarco/ER Ca(2+) ATPase, ER Ca(2+) release channels, inositol 1,4,5-trisphosphate receptor channel, ryanodine receptor, and Ca(2+)-binding proteins inside of the ER lumen. Alterations in ER homeostasis trigger ER Ca(2+) depletion and ER stress, which have been associated with the development of a variety of diseases. In addition, recent studies have highlighted the role of ER Ca(2+) imbalance caused by dysfunction of sarco/ER Ca(2+) ATPase, ryanodine receptor, and inositol 1,4,5-trisphosphate receptor channel in various kidney diseases. Despite progress in the understanding of the importance of these ER Ca(2+) channels, pumps, and binding proteins in the pathogenesis of kidney disease, treatment is still lacking. This mini-review is focused on: i) Ca(2+) homeostasis in the ER, ii) ER Ca(2+) dyshomeostasis and apoptosis, and iii) altered ER Ca(2+) homeostasis in kidney disease, including podocytopathy, diabetic nephropathy, albuminuria, autosomal dominant polycystic kidney disease, and ischemia/reperfusion-induced acute kidney injury.

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