Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Exp Biol Med (Maywood). 2021 Feb;246(3):305-316. doi: 10.1177/1535370220975207. Epub 2020 Nov 29.
Research conducted over the last two decades has dramatically advanced the understanding of store-operated calcium channels (SOCC) and their impact on renal function. Kidneys contain many types of cells, including those specialized for glomerular filtration (fenestrated capillary endothelium, podocytes), water and solute transport (tubular epithelium), and regulation of glomerular filtration and renal blood flow (vascular smooth muscle cells, mesangial cells). The highly integrated function of these myriad cells effects renal control of blood pressure, extracellular fluid volume and osmolality, electrolyte balance, and acid-base homeostasis. Many of these cells are regulated by Ca signaling. Recent evidence demonstrates that SOCCs are major Ca entry portals in several renal cell types. SOCC is activated by depletion of Ca stores in the sarco/endoplasmic reticulum, which communicates with plasma membrane SOCC via the Ca sensor Stromal Interaction Molecule 1 (STIM1). Orai1 is recognized as the main pore-forming subunit of SOCC in the plasma membrane. Orai proteins alone can form highly Ca selective SOCC channels. Also, members of the Transient Receptor Potential Canonical (TRPC) channel family are proposed to form heteromeric complexes with Orai1 subunits, forming SOCC with low Ca selectivity. Recently, Ca entry through SOCC, known as store-operated Ca entry (SOCE), was identified in glomerular mesangial cells, tubular epithelium, and renovascular smooth muscle cells. The physiological and pathological relevance and the characterization of SOCC complexes in those cells are still unclear. In this review, we summarize the current knowledge of SOCC and their roles in renal glomerular, tubular and vascular cells, including studies from our laboratory, emphasizing SOCE regulation of fibrotic protein deposition. Understanding the diverse roles of SOCE in different renal cell types is essential, as SOCC and its signaling pathways are emerging targets for treatment of SOCE-related diseases.
在过去的二十年中，对钙库操纵性钙通道（SOCC）及其对肾功能影响的研究取得了显著进展。肾脏包含多种细胞类型，包括专门用于肾小球过滤（有孔毛细血管内皮细胞、足细胞）、水和溶质转运（肾小管上皮细胞）以及调节肾小球过滤和肾血流量（血管平滑肌细胞、系膜细胞）的细胞。这些众多细胞的高度整合功能影响着肾脏对血压、细胞外液体积和渗透压、电解质平衡和酸碱平衡的控制。许多这些细胞都受到 Ca 信号的调节。最近的证据表明，SOCC 是几种肾细胞类型中的主要 Ca 进入通道。SOCC 通过肌浆网/内质网 Ca 储存耗竭激活，通过 Ca 传感器基质相互作用分子 1（STIM1）与质膜 SOCC 进行通讯。Orai1 被认为是质膜中 SOCC 的主要孔形成亚基。Orai 蛋白本身可以形成高度 Ca 选择性的 SOCC 通道。此外，瞬时受体电位经典（TRPC）通道家族的成员被提议与 Orai1 亚基形成异源二聚体复合物，形成 Ca 选择性低的 SOCC。最近，通过 SOCC 的 Ca 进入，即钙库操纵性钙内流（SOCE），在肾小球系膜细胞、肾小管上皮细胞和肾血管平滑肌细胞中被鉴定出来。这些细胞中 SOCC 复合物的生理病理相关性和特征仍不清楚。在这篇综述中，我们总结了 SOCC 的最新知识及其在肾小球、肾小管和血管细胞中的作用，包括我们实验室的研究，强调了 SOCE 对纤维化蛋白沉积的调节。了解 SOCE 在不同肾细胞类型中的不同作用至关重要，因为 SOCC 和其信号通路是治疗与 SOCE 相关疾病的新兴靶点。
