The kidney is the key organ responsible for maintaining the body\'s water and electrolyte homeostasis. About 99% of the primary urine filtered from the Bowman\'s capsule is reabsorbed along various renal tubules every day, with only 1-2 L of urine excreted. Aquaporins (AQPs) play a vital role in water reabsorption in the kidney. Currently, a variety of molecules are found to be involved in the process of urine concentration by regulating the expression or activity of AQPs, such as antidiuretic hormone, renin-angiotensin-aldosterone system (RAAS), prostaglandin, and several nuclear receptors. As the main bile acid receptors, farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor 1 (TGR5) play important roles in bile acid, glucose, lipid, and energy metabolism. In the kidney, FXR and TGR5 exhibit broad expression across all segments of renal tubules, and their activation holds significant therapeutic potential for numerous acute and chronic kidney diseases through alleviating renal lipid accumulation, inflammation, oxidative stress, and fibrosis. Emerging evidence has demonstrated that the genetic deletion of FXR or TGR5 exhibits increased basal urine output, suggesting that bile acid receptors play a critical role in urine concentration. Here, we briefly summarize the function of bile acid receptors in renal water reabsorption and urine concentration.

A solitary functioning kidney (SFK) from birth predisposes to hypertension and kidney dysfunction, and this may be associated with impaired fluid and sodium homeostasis. Brief and early angiotensin-converting enzyme inhibition (ACEi) in a sheep model of SFK delays onset of kidney dysfunction. We hypothesized that modulation of the renin-angiotensin system via brief postnatal ACEi in SFK would reprogram renal sodium and water handling. Here, blood pressure (BP), kidney haemodynamics and kidney excretory function were examined in response to an isotonic saline load (0.13 ml/kg/min, 180 min) at 20 months of age in SFK (fetal unilateral nephrectomy at 100 days gestation; term 150 days), sham and SFK+ACEi sheep (ACEi in SFK 4-8 weeks of age). Basal BP was higher in SFK than sham (∼13 mmHg), and similar between SFK and SFK+ACEi groups. Saline loading caused a small increase in BP (∼3-4 mmHg) the first 2 h in SFK and sham sheep but not SFK+ACEi sheep. Glomerular filtration rate did not change in response to saline loading. Total sodium excretion was similar between groups. Total urine excretion was similar between SFK and sham animals but was ∼40% less in SFK+ACEi animals compared with SFK animals. In conclusion, the present study indicates that water homeostasis in response to a physiological challenge is attenuated at 20 months of age by brief early life ACEi in SFK. Further studies are required to determine if ACEi in early life in children with SFK could compromise fluid homeostasis later in life.

Adequate hydration is essential for the maintenance of health and physiological functions in humans. However, many older adults do not maintain adequate hydration, which is under-recognized and poorly managed. Older adults are more vulnerable to dehydration, especially those living with multiple chronic diseases. Dehydration is associated with adverse health outcomes in older adults, and acts as an independent factor of the hospital length of stay, readmission, intensive care, in-hospital mortality, and poor prognosis. Dehydration is a prevalent health problem in older adults, accounting for substantial economic and social burden. This review attempts to provide current knowledge of hydration including patterns of body water turnover, the complex mechanisms behind water homeostasis, the effects of dehydration on the health of the body, and practical guidance for low-intake dehydration in older adults.

Migration is one of the most energy-demanding tasks in avian life cycle. Many birds might not have sufficient fuel stores to cover long distances, so they must stop to rest and refuel at stopover sites, especially after the crossing of large ecological barriers. There, birds undergo several behavioral, morphological, and physiological trait adjustments to recover from and prepare for their journey; however, regulation of such processes at the molecular level remains largely unknown. In this study, we used transcriptomic information from the whole blood of migrating garden warblers (Sylvia borin) to identify key regulatory pathways related to adaptations for migration. Birds were temporarily caged during spring migration stopover and then sampled twice at different refueling states (lean vs. fat), reflecting different migratory stages (stopover arrival vs. departure) after the crossing of an extended ecological barrier. Our results show that top expressed genes during migration are involved in important pathways regarding adaptations to migration at high altitudes such as increase of aerobic capacity and angiogenesis. Gene expression profiles largely reflected the two experimental conditions with several enzymes involved in different aspects of metabolic activity being differentially expressed between states providing several candidate genes for future functional studies. Additionally, we identified several hub genes, upregulated in lean birds that could be involved in the extraordinary phenotypic flexibility in organ mass displayed by avian migrants. Finally, our approach provides novel evidence that regulation of water homeostasis may represent a significant adaptive mechanism, allowing birds to conserve water during long-distance flight, mainly through protein catabolism.

Persistent high temperature decreases the yield and quality of crops, including many important herbs. White clover (Trifolium repens) is a perennial herb with high feeding and medicinal value, but is sensitive to temperatures above 30 °C. The present study was conducted to elucidate the impact of changes in endogenous γ-aminobutyric acid (GABA) level by exogenous GABA pretreatment on heat tolerance of white clover, associated with alterations in endogenous hormones, antioxidant metabolism, and aquaporin-related gene expression in root and leaf of white clover plants under high-temperature stress. Our results reveal that improvement in endogenous GABA level in leaf and root by GABA pretreatment could significantly alleviate the damage to white clover during high-temperature stress, as demonstrated by enhancements in cell membrane stability, photosynthetic capacity, and osmotic adjustment ability, as well as lower oxidative damage and chlorophyll loss. The GABA significantly enhanced gene expression and enzyme activities involved in antioxidant defense, including superoxide dismutase, catalase, peroxidase, and key enzymes of the ascorbic acid-glutathione cycle, thus reducing the accumulation of reactive oxygen species and the oxidative injury to membrane lipids and proteins. The GABA also increased endogenous indole-3-acetic acid content in roots and leaves and cytokinin content in leaves, associated with growth maintenance and reduced leaf senescence under heat stress. The GABA significantly upregulated the expression of PIP1-1 and PIP2-7 in leaves and the TIP2-1 expression in leaves and roots under high temperature, and also alleviated the heat-induced inhibition of PIP1-1, PIP2-2, TIP2-2, and NIP1-2 expression in roots, which could help to improve the water transportation and homeostasis from roots to leaves. In addition, the GABA-induced aquaporins expression and decline in endogenous abscisic acid level could improve the heat dissipation capacity through maintaining higher stomatal opening and transpiration in white clovers under high-temperature stress.

Aquaporins (AQPs) are integral membrane proteins and found in all living organisms from bacteria to human. AQPs mainly involved in the transmembrane diffusion of water as well as various small solutes in a bidirectional manner are widely distributed in various human tissues. Human contains 13 AQPs (AQP0-AQP12) which are divided into three sub-classes namely orthodox aquaporin (AQP0, 1, 2, 4, 5, 6, and 8), aquaglyceroporin (AQP3, 7, 9, and 10) and super or unorthodox aquaporin (AQP11 and 12) based on their pore selectivity. Human AQPs are functionally diverse, which are involved in wide variety of non-infectious diseases including cancer, renal dysfunction, neurological disorder, epilepsy, skin disease, metabolic syndrome, and even cardiac diseases. However, the association of AQPs with infectious diseases has not been fully evaluated. Several studies have unveiled that AQPs can be regulated by microbial and parasitic infections that suggest their involvement in microbial pathogenesis, inflammation-associated responses and AQP-mediated cell water homeostasis. This review mainly aims to shed light on the involvement of AQPs in infectious and non-infectious diseases and potential AQPs-target modulators. Furthermore, AQP structures, tissue-specific distributions and their physiological relevance, functional diversity and regulations have been discussed. Altogether, this review would be useful for further investigation of AQPs as a potential therapeutic target for treatment of infectious as well as non-infectious diseases.

The apelin receptor (APJ) is a member of the family A of G-protein-coupled receptors (GPCRs) and is involved in range of physiological and pathological functions, including fluid homeostasis, anxiety, and depression, as well as cardiovascular and metabolic disorders. APJ was classically described as a monomeric transmembrane receptor that forms a ternary complex together with its ligand and associated G proteins. More recently, increasing evidence indicates that APJ may interact with other GPCRs to form heterodimers, which may selectively modulate distinct intracellular signal transduction pathways. Besides, the apelin/APJ system plays important roles in the physiology and pathophysiology of several organs, including regulation of blood pressure, cardiac contractility, angiogenesis, metabolic balance, and cell proliferation, apoptosis, or inflammation. Additionally, the apelin/APJ system is widely expressed in the central nervous system, especially in neurons and oligodendrocytes. This article reviews the role of apelin/APJ in energy metabolism and water homeostasis. Compared with the traditional diuretics, apelin exerts a positive inotropic effect on the heart, while increases water excretion. Therefore, drugs targeting apelin/APJ system undoubtedly provide more therapeutic options for patients with congestive heart failure accompanied with hyponatremia. To provide more precise guidance for the development of clinical drugs, further in-depth studies are warranted on the metabolism and signaling pathways associated with apelin/APJ system.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic disorder belonging to the group of vacuolating leukodystrophies. It is characterized by megalencephaly, loss of motor functions, epilepsy, and mild mental decline. In brain biopsies of MLC patients, vacuoles were observed in myelin and in astrocytes surrounding blood vessels. It is mainly caused by recessive mutations in MLC1 and HEPACAM (also called GLIALCAM) genes. These disease variants are called MLC1 and MLC2A with both types of patients sharing the same clinical phenotype. Besides, dominant mutations in HEPACAM were also identified in a subtype of MLC patients (MLC2B) with a remitting phenotype. MLC1 and GlialCAM proteins form a complex mainly expressed in brain astrocytes at the gliovascular interface and in Bergmann glia at the cerebellum. Both proteins regulate several ion channels and transporters involved in the control of ion and water fluxes in glial cells, either directly influencing their location and function, or indirectly regulating associated signal transduction pathways. However, the MLC1/GLIALCAM complex function and the related pathological mechanisms leading to MLC are still unknown. It has been hypothesized that, in MLC, the role of glial cells in brain ion homeostasis is altered in both physiological and inflammatory conditions. There is no therapy for MLC patients, only supportive treatment. As MLC2B patients show an MLC reversible phenotype, we speculated that the phenotype of MLC1 and MLC2A patients could also be mitigated by the re-introduction of the correct gene even at later stages. To prove this hypothesis, we injected in the cerebellar subarachnoid space of Mlc1 knockout mice an adeno-associated virus (AAV) coding for human MLC1 under the control of the glial-fibrillary acidic protein promoter. MLC1 expression in the cerebellum extremely reduced myelin vacuolation at all ages in a dose-dependent manner. This study could be considered as the first preclinical approach for MLC. We also suggest other potential therapeutic strategies in this review.

There are considerable variations in the percentage loss of hydraulic conductivity (PLC) at mid-day minimum water potential among and within species, but the underpinning mechanism(s) are poorly understood. This study tested the hypothesis that plants can regulate leaf specific hydraulic conductance (K l) via precise control over PLC under variable ΔΨ (water potential differential between soil and leaf) conditions to maintain the -m/b constant (-m: the sensitivity of stomatal conductance to VPD; b: reference stomatal conductance at 1.0 kPa VPD), where VPD is vapor pressure deficit. We used Populus euphratica, a phreatophyte species distributed in the desert of Northwestern China, to test the hypothesis. Field measurements of VPD, stomatal conductance (g s), g s responses to VPD, mid-day minimum leaf water potential (Ψ lmin), and branch hydraulic architecture were taken in late June at four sites along the downstream of Tarim River at the north edge of the Taklamakan desert. We have found that: 1) the -m/b ratio was almost constant (=0.6) across all the sites; 2) the average Ψ 50 (the xylem water potential with 50% loss of hydraulic conductivity) was -1.63 MPa, and mid-day PLC ranged from 62 to 83%; 3) there were tight correlations between Ψ 50 and wood density/leaf specific hydraulic conductivity (k l) and between specific hydraulic conductance sensitivity to water potential [d(k s)/dln(-Ψ)] and specific hydraulic conductivity (k s). A modified hydraulic model was applied to investigate the relationship between g s and VPD under variable ΔΨ and K l conditions. It was concluded that P. euphratica was able to control PLC in order to maintain a relatively constant -m/b under different site conditions. This study demonstrated that branchlet hydraulic architecture and stomatal response to VPD were well coordinated in order to maintain relatively water homeostasis of P. euphratica in the desert. Model simulations could explain the wide variations of PLC across and within woody species that are often observed in the field.

The distal nephron and collecting duct segments of the mammalian kidney consist of intercalated cell types intermingled among principal cell types. Notch signaling ensures that a sufficient number of cells select a principal instead of an intercalated cell fate. However, the precise mechanisms by which Notch signaling patterns the distal nephron and collecting duct cell fates is unknown. Here we observed that Hes1, a direct target of Notch signaling pathway, is required within the mouse developing collecting ducts for repression of Foxi1 expression, an essential intercalated cell specific transcription factor. Interestingly, inactivation of Foxi1 in Hes1-deficient collecting ducts rescues the deficiency in principal cell fate selection, overall urine concentrating deficiency, and reduces the occurrence of hydronephrosis. However, Foxi1 inactivation does not rescue the reduction in expression of all principal cell genes in the Hes1-deficient kidney collecting duct cells that select the principal cell fate. Additionally, suppression of Notch/Hes1 signaling in mature principal cells reduces principal cell gene expression without activating Foxi1. We conclude that Hes1 is a Notch signaling target that is essential for normal patterning of the collecting ducts with intermingled cell types by repressing Foxi1, and for maintenance of principal cell gene expression independent of repressing Foxi1.