Plasticity of renal endocrine function

Abstract

The kidneys are important endocrine organs. They secrete humoral factors, such as calcitriol, erythropoietin, klotho, and renin into the circulation, and therefore, they are essentially involved in the regulation of a variety of processes ranging from bone formation to erythropoiesis. The endocrine functions are established by cells, such as proximal or distal tubular cells, renocortical interstitial cells, or mural cells of afferent arterioles. These endocrine cells are either fixed in number, such as tubular cells, which individually and gradually upregulate or downregulate hormone production, or they belong to a pool of cells, which display a recruitment behavior, such as erythropoietin-and reninproducing cells. In the latter case, regulation of humoral function occurs via (de)recruitment of active endocrine cells. As a consequence renin-and erythropoietin-producing cells in the kidney show a high degree of plasticity by reversibly switching between distinct cell states. In this review, we will focus on the characteristics of renin-and of erythropoietin-producing cells, especially on their origin and localization, their reversible transformations, and the mediators, which are responsible for transformation. Finally, we will discuss a possible interconversion of renin and erythropoietin expression.calcitriol; erythropoietin; klotho; renin THE KIDNEYS FULFILL A VARIETY of functions, such as elimination of waste products of metabolism, regulation of fluid volume, and electrolyte concentrations and acid-base balance. Besides these excretory and homeostatic functions, the kidneys are endocrine organs essentially involved in the regulation of bone mineralization, blood pressure, and erythropoiesis. Thereto, the kidneys produce and secrete the hormones calcitriol, erythropoietin (EPO), klotho, and renin.Klotho, which exists in a membranous and a secreted form, regulates calcium and phosphate homeostasis (67, 83,129), thus contributing to bone mineralization. Membrane klotho functions mainly as a coreceptor for fibroblast growth factor (FGF) 23 (85, 178), which causes phosphaturia (85) and decreases circulating calcitriol levels (187) and renal phosphate resorption, resulting in reduced plasma phosphate levels. In its soluble form (66, 110), klotho mediates enhanced Ca 2ϩ (re)absorption in the kidney and in the intestine, by activating TRPV5 and TRPV6 (21, 23) channels. Missense mutations or deficiency of klotho result in hyperphosphatemia, hypercalcemia, and vascular calcification (64, 84,95,157).Calcitriol (34,35,138), the physiologically active form of vitamin D, contributes to bone mineralization by regulating homeostasis of calcium and phosphate through acting on the intestinal tract and the kidneys. Besides its role in regulation of calcium and phosphate homeostasis, calcitriol contributes to erythropoiesis (5, 48), as well as the activity of monocytes and macrophages (30). In contrast, proliferation and activity of T-lymphocytes and, thus, the adaptive immunity are suppressed by calcitriol (30). Vitamin D defi...

Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3 signaling pathway

“…Although in low dose, it can help strengthen bones and prevent dental caries, however, for instance, due to the wide usage of F in industrial processes, accumulating evidence showed that excessive F exposure causes a variety of adverse effects on soft tissues 2 . The kidney is a multifunctional organ that plays a role in the endocrine, excretory, and hematopoietic systems 3, 4 . It plays an important role in maintaining the homeostasis of the body by selectively excreting or retaining various substances on the basis of specific body needs.…”

Zebrafish mesonephric renin cells are functionally conserved and comprise two distinct morphological populations

“…The relationship of renin-expressing cells to smooth muscle cells (SMC) expressing (acta2) and pericytes expressing (pdgfrb) was analyzed using Tg(ren:LifeAct-RFP, acta2:EGFP) and Tg(ren:LifeAct-RFP, pdgfrb:EGFP) fish, respectively. With an inverse relationship to smooth muscle actin (SMA), mammalian renin expression increases along metanephric afferent arterioles with decreasing distance from the glomerulus (35,36,48,62). In zebrafish, all renin-expressing cells coexpressed acta2:EGFP (Fig.…”

Erythropoietin between therapy and doping : Two sides of the same coin

“…Anaemia in renal insufficiency is multifactorial, but mainly a consequence of decreased erythropoietin production, due to EPO-producing fibroblasts transdifferentiation into myofibroblasts, predominantly collagen-secreting cells (7,20). This occurs under the influence of proinflammatory cytokines, TNFα and TGFβ.…”

“…Important role here play hypoxia inducible factors 1 and 2 (HIF 1 and 2) which induce erythropoietin gene transcription (1,6). These are ubiquitary enzymes, but HIF 2 is more present in kidney and liver cells, and hence more specific for EPO gene transcription (7,8). Non-HIF pathways that can alter EPO production include kinase C, GATA-2, nuclear factor kappa B (NFB) pathways (7,9).…”

“…These are ubiquitary enzymes, but HIF 2 is more present in kidney and liver cells, and hence more specific for EPO gene transcription (7,8). Non-HIF pathways that can alter EPO production include kinase C, GATA-2, nuclear factor kappa B (NFB) pathways (7,9). Baseline EPO concentration can raise up to 1000 fold in hypoxic conditions (10).…”