Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland.
J Cell Physiol. 2021 Oct;236(10):7176-7185. doi: 10.1002/jcp.30368. Epub 2021 Mar 19.
The sodium-dependent phosphate transporters Pit 1 and Pit 2 belong to the solute carrier 20 (SLC20) family of membrane proteins. They are ubiquitously distributed in the human body. Their crucial function is the intracellular transport of inorganic phosphate (Pi) in the form of H PO . They are one of the main elements in maintaining physiological phosphate homeostasis. Recent data have emerged that indicate novel roles of Pit 1 and Pit 2 proteins besides the well-known function of Pi transporters. These membrane proteins are believed to be precise phosphate sensors that mediate Pi-dependent intracellular signaling. They are also involved in insulin signaling and influence cellular insulin sensitivity. In diseases that are associated with hyperphosphatemia, such as diabetes and chronic kidney disease (CKD), disturbances in the function of Pit 1 and Pit 2 are observed. Phosphate transporters from the SLC20 family participate in the calcification of soft tissues, mainly blood vessels, during the course of CKD. The glomerulus and podocytes therein can also be a target of pathological calcification that damages these structures. A few studies have demonstrated the development of Pi-dependent podocyte injury that is mediated by Pit 1 and Pit 2. This paper discusses the role of Pit 1 and Pit 2 proteins in podocyte function, mainly in the context of the development of pathological calcification that disrupts permeability of the renal filtration barrier. We also describe the mechanisms that may contribute to podocyte damage by Pit 1 and Pit 2.
钠依赖性磷酸盐转运蛋白 Pit1 和 Pit2 属于溶质载体 20(SLC20)家族的膜蛋白。它们在人体中广泛分布。其关键功能是以 HPO 的形式在细胞内转运无机磷酸盐(Pi)。它们是维持生理磷酸盐稳态的主要元素之一。最近的数据表明,Pit1 和 Pit2 蛋白除了众所周知的 Pi 转运蛋白功能外,还具有新的作用。这些膜蛋白被认为是精确的磷酸盐传感器,介导 Pi 依赖性细胞内信号转导。它们还参与胰岛素信号转导并影响细胞胰岛素敏感性。在与高磷酸盐血症相关的疾病中,如糖尿病和慢性肾脏病(CKD),观察到 Pit1 和 Pit2 功能的紊乱。SLC20 家族的磷酸盐转运体参与 CKD 过程中软组织(主要是血管)的钙化。肾小球和足细胞也可能成为病理性钙化的靶标,从而损害这些结构。一些研究已经证明了由 Pit1 和 Pit2 介导的 Pi 依赖性足细胞损伤的发生。本文讨论了 Pit1 和 Pit2 蛋白在足细胞功能中的作用,主要是在破坏肾脏滤过屏障通透性的病理性钙化的背景下。我们还描述了 Pit1 和 Pit2 可能导致足细胞损伤的机制。