Expression Of Aquaporin Research Articles

Bifidobacterium bifidum CCFM1163 Alleviated Cathartic Colon by Regulating the Intestinal Barrier and Restoring Enteric Nerves.

Cathartic colon (CC), a type of slow-transit constipation caused by the long-term use of stimulant laxatives, does not have a precise and effective treatment. This study aimed to evaluate the ability of Bifidobacterium bifidum CCFM1163 to relieve CC and to investigate its underlying mechanism. Male C57BL/6J mice were treated with senna extract for 8 weeks, followed by a 2-week treatment with B. bifidum CCFM1163. The results revealed that B. bifidum CCFM1163 effectively alleviated CC symptoms. The possible mechanism of B. bifidum CCFM1163 in relieving CC was analyzed by measuring the intestinal barrier and enteric nervous system (ENS)-related indices and establishing a correlation between each index and gut microbiota. The results indicated that B. bifidum CCFM1163 changed the gut microbiota by significantly increasing the relative abundance of Bifidobacterium, Faecalibaculum, Romboutsia, and Turicibacter as well as the content of short-chain fatty acids, especially propionic acid, in the feces. This increased the expression of tight junction proteins and aquaporin 8, decreased intestinal transit time, increased fecal water content, and relieved CC. In addition, B. bifidum CCFM1163 also increased the relative abundance of Faecalibaculum in feces and the expression of enteric nerve marker proteins to repair the ENS, promote intestinal motility, and relieve constipation.

Fu Brick Tea Alleviates Constipation via Regulating the Aquaporins-Mediated Water Transport System in Association with Gut Microbiota.

This study aimed to investigate the amendatory effects of Fu brick tea aqueous extract (FTE) on constipation and its underlying molecular mechanism. The administration of FTE by oral gavage (100 and 400 mg/kg·bw) for 5 weeks significantly increased fecal water content, improved difficult defecation, and enhanced intestinal propulsion in loperamide (LOP)-induced constipated mice. FTE also reduced colonic inflammatory factors, maintained the intestinal tight junction structure, and inhibited colonic Aquaporins (AQPs) expression, thus normalizing the intestinal barrier and colonic water transport system of constipated mice. 16S rRNA gene sequence analysis results indicated that two doses of FTE increased the Firmicutes/Bacteroidota (F/B) ratio at the phylum level and increased the relative abundance of Lactobacillus from 5.6 ± 1.3 to 21.5 ± 3.4% and 28.5 ± 4.3% at the genus level, subsequently resulting in a significant elevation of colonic contents short-chain fatty acids levels. The metabolomic analysis demonstrated that FTE improved levels of 25 metabolites associated with constipation. These findings suggest that Fu brick tea has the potential to alleviate constipation by regulating gut microbiota and its metabolites, thereby improving the intestinal barrier and AQPs-mediated water transport system in mice.

Combination of Merocel sponge with Lipopolysaccharide to establish rat rhinosinusitis model

ObjectiveThe study aimed to investigate the feasibility of establishing rhinosinusitis model in rats combinated with Lipopolysaccharide (LPS) and merocel sponge. MethodsSD (Sprague Dawley) rats that underwent nasal obstruction using Merocel sponge packing, rats with LPS instillation alone, and rats with both nasal obstruction and LPS instillation were used to establish rat models of rhinosinusitis. After the models were established, the nasal symptoms of rats were recorded, the histopathological examination and Transmission Electron Microscopy (TME) of the sinus tissue were performed and the levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) in the blood were also analyzed. The expressions of Aquaporin-5 (AQP5), Occludin, Toll-Like Receptor-4 (TLR4), Medullary differentiation factor 88 (MyD88) and phosphorylated (p)-p65 protein were detected by Western blot to evaluate the effect and mechanism of the experimental models. ResultsWe found that compared with the control group and LPS group, the sinusitis symptom scores in the Merocel sponge combined with LPS group were significantly increased; the respiratory epithelia of the maxillary sinus were degenerated, cilia were detached, and even inflammatory cell infiltration occurred; the levels of TNF-α and IL-6 were increased; the expression of AQP5 and Occludin protein was decreased; and the expressions of TLR4, MyD88, and p-p65 protein were increased. ConclusionFor the first time, we successfully established a rat rhinosinusitis model using Merocel sponge with LPS and explored the possible mechanism of LPS action.

Onion plants (Allium cepa L.) react differently to salinity levels according to the regulation of aquaporins

As salinity is one of the main environmental stresses that reduces the growth and productivity of crops by reducing water uptake and transport, in this work, we associated the physiological tolerance response of onion to increased NaCl concentration (from 25, 50, 75, to 100 mM) with the expression of aquaporins. Measurements of transpiration, gas exchange and nutrients content in leaf, roots and bulb tissues were determined in relation to the expression of PIP2, PIP1, and TIP2 aquaporin genes. The results indicated a significant decrease in growth in leaves, roots and bulbs only when 50 mM NaCl was applied. However, this was not correlated with the rest of the parameters, such as transpiration, number of stomata, osmotic potential, or chlorophyll concentration. In this way, the finding that the decreases in Mn, Zn and B observed in leaves, roots and bulbs at 50 mM NaCl were related to the expression of aquaporins, leaded to propose two phases of responses to salinity depending on level of NaCl. Therefore, the activation of PIP2 at 75 mM, in relation to Zn uptake, is proposed as relevant in the response of onion to high salinity.

Activating Blood Circulation, Anti-Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling.

Leonurus japonicus Houtt. has been traditionally used to treat many ailments. This study evaluated the activating blood circulation, anti-inflammatory, and diuretic effects of L. japonicus extract (LJ) and identified its phytochemicals. In this work, the phytochemicals in LJ were identified using liquid chromatography mass spectrometry. Rats were randomly assigned to three groups (n=8): Control group was treated with saline, while the Model group (saline) and LJ group (426 mg/kg) had induced traumatic injury. All rats were treated with once by daily oral gavage for one week. The biochemical indices and protein expression were measured. Herein, 79 constituents were identified in LJ, which were effective in elevating body weight, food consumption, water intake, and urinary excretion volume, as well as in ameliorating traumatic muscle tissues in model rats. In addition, LJ prominently decreased the contents of plasma viscosity, platelet aggregation rate, thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen, thromboxane B2 (TXB2), TXB2/6-keto-prostaglandin F1α (6-keto-PGF1α), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tissue-type PA (t-PA), and PAI-1/u-PA, while significantly increasing antithrombin III, 6-keto-PGF1α, and t-PA contents. Furthermore, LJ notably inhibited tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, angiotensin II, antidiuretic hormone, aldosterone, aquaporin 1 (AQP1), AQP2, and AQP3 levels, and markedly elevating IL-10 and natriuretic peptide levels. Finally, LJ markedly reduced the protein expression of AQP1, AQP2, and AQP3 compared to the model group. Collectively, LJ possessed prominent activating blood circulation, anti-inflammatory, and diuretic effects, thus supporting the clinical application of L. japonicus.

AQP1 in the Gastrointestinal Tract of Mice: Expression Pattern and Impact of AQP1 Knockout on Colonic Function.

Aquaporin 1 (AQP1) is one of thirteen known mammalian aquaporins. Its main function is the transport of water across cell membranes. Lately, a role of AQP has been attributed to other physiological and pathological functions including cell migration and peripheral pain perception. AQP1 has been found in several parts of the enteric nervous system, e.g., in the rat ileum and in the ovine duodenum. Its function in the intestine appears to be multifaceted and is still not completely understood. The aim of the study was to analyze the distribution and localization of AQP1 in the entire intestinal tract of mice. AQP1 expression was correlated with the hypoxic expression profile of the various intestinal segments, intestinal wall thickness and edema, as well as other aspects of colon function including the ability of mice to concentrate stools and their microbiome composition. AQP1 was found in a specific pattern in the serosa, the mucosa, and the enteric nervous system throughout the gastrointestinal tract. The highest amount of AQP1 in the gastrointestinal tract was found in the small intestine. AQP1 expression correlated with the expression profiles of hypoxia-dependent proteins such as HIF-1α and PGK1. Loss of AQP1 through knockout of AQP1 in these mice led to a reduced amount of bacteroidetes and firmicutes but an increased amount of the rest of the phyla, especially deferribacteres, proteobacteria, and verrucomicrobia. Although AQP-KO mice retained gastrointestinal function, distinct changes regarding the anatomy of the intestinal wall including intestinal wall thickness and edema were observed. Loss of AQP1 might interfere with the ability of the mice to concentrate their stool and it is associated with a significantly different composition of the of the bacterial stool microbiome.

The Rootstock Genotypes Determine Drought Tolerance by Regulating Aquaporin Expression at the Transcript Level and Phytohormone Balance.

Grapevine rootstocks may supply water to the scion according to the transpiration demand, thus modulating plant responses to water deficit, but the scion variety can alter these responses, as well. The rootstock genotypes' effect on the scion physiological response, aquaporin expression, and hormone concentrations in the xylem and the leaf was assessed under well watered (WW) and water stress (WS) conditions. Under WW, vines grafted onto 1103P and R110 rootstocks (the more vigorous and drought-tolerant) showed higher photosynthesis (AN), stomatal conductance (gs), and hydraulic conductance (Khplant) compared with the less vigorous and drought-sensitive rootstock (161-49C), while under WS, there were hardly any differences between vines depending on the rootstock grafted. Besides, stomatal traits were affected by drought, which was related to gs, but not by the rootstock. Under WS conditions, all VvPIP and VvTIP aquaporins were up-regulated in the vines grafted onto 1103P and down-regulated in the ones grafted onto 161-49C. The 1103P capability to tolerate drought was enhanced by the up-regulation of all VvPIP and VvTIP aquaporins, lower ABA synthesis, and higher ACC/ABA ratios in leaves during WS compared with 161-49C. It was concluded that, under WW conditions, transpiration and stomatal control were rootstock-dependent. However, under WS conditions, alterations in the molecular components of water transport and hormone concentration of the scion resulted in similar gas exchange values in the studied scions grafted onto different rootstocks.

Cover Image

The cover image is based on the Original Article Effect of partially hydrolyzed guar gum on the expression of aquaporin-3 in the colon by Risako Kon et al., https://doi.org/10.1002/fsn3.3150

Synergetic effect of water deficit and arbuscular mycorrhizal symbiosis on theexpression of aquaporins in wheat (Triticum aestivum L.) roots: insights from NGS RNA-sequencing.

The online version contains supplementary material available at 10.1007/s12298-023-01285-w.

A novel and low-toxic peptide DR3penA alleviates pulmonary fibrosis by regulating the MAPK/miR-23b-5p/AQP5 signaling axis.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

Aquaporin 5 (AQP5) expression in breast cancer and its clinicopathological characteristics.

The role of aquaporin water channels (AQPs) has become an area of great interest in human carcinogenesis. In this report, we have demonstrated the expression of AQP5 in breast cancer by analyzing 591 tissue samples with 7-year follow-ups. By immunochemistry analysis, AQP5 overexpression was observed in 36% (212/591 cases). Then, we have focused on the clinicopathologic variables among cancer tissue samples with strong AQP5 expression (3+ expression, 60/591 cases). The strong AQP5 expression was positively correlated with tumor grade in BCs (p<0.001) and was more frequent in ER/PR-negative BCs than positive ones (14.9% vs. 3.3% and 13.1% vs. 4.8%, respectively, both p<0.001), while Her2/neu-positive status was positively correlated with strong expression of AQP5 (p = 0.005). Of note, breast cancer patients with positive AQP expression (212/591 cases) showed a less favorable breast cancer specific survival rate over 7 years of follow and we further conclude that AQP5 expression is an independent molecular marker associated with worse clinical outcomes. By fluorescence in situ hybridization (FISH), we have identified evidence of gene amplification in 3 of 30 readable breast cancer and further conclude that, in breast cancer, at least some part of AQP5 overexpression is associated with an aberration in the genome level.

Arbuscular mycorrhizal fungi inoculation impacts expression of aquaporins and salt overly sensitive genes and enhances tolerance of salt stress in tomato

Arbuscular mycorrhizal fungi (AMF) that establish reciprocal symbiosis with plant roots can enhance resistance to various stresses, including salt stress, but relevant mechanisms, especially at the molecular level, are scarce. The objective of this study was to analyze the effect of an arbuscular mycorrhizal fungus Paraglomus occultum on plant growth, leaf gas exchange, and expression of plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs) and salt overly sensitive (SOS) genes in tomato under salt (150 mmol/L NaCl) and non-salt stress. Salt stress for 4 weeks inhibited root colonization rate of P. occultum and soil hyphal length by 0.21- and 0.57-fold, respectively. Salt stress also inhibited plant growth performance and leaf gas exchange, while inoculation with P. occultum significantly enhanced them under salt and non-salt stress conditions. AMF showed diverse regulation of root SlPIPs and SlTIPs expression, among which under salt stress, SlPIP1;2, SlPIP1;5, SlPIP2;1, SlPIP2;6, SlPIP2;9, SlPIP2;10, SlTIP2;2, SlTIP3;2, and SlTIP5;1 were up-regulated by AMF colonization, and SlPIP1;7, SlPIP2;5, SlPIP2;8, SlPIP2;11, SlPIP2;12, SlTIP2;3, and SlTIP3;1 were down-regulated, accompanied by no change in SlPIP1;1, SlPIP1;3, SlPIP2;4, SlTIP1;1, SlTIP1;2, SlTIP1;3, SlTIP2;1, and SlTIP2;5. Interestingly, salt stress inhibited the expression of SlSOS1 and SlSOS2 in non-mycorrhizal plants, while it increased the expression of SlSOS1 and SlSOS2 in mycorrhizal plants. AMF colonization down-regulated expression of SlSOS1 and SlSOS2 under non-salt stress while up-regulated expression of SlSOS1 and SlSOS2 under salt stress. It was concluded that AMF inoculation impacted the expression of stress-responsive genes, especially SOS1 and SOS2, and enhanced salt resistance of tomato.Graphical

Aquaporin-mediated dysregulation of cell migration in disease states.

Dysregulated cell migration and invasion are hallmarks of many disease states. This dysregulated migratory behavior is influenced by the changes in expression of aquaporins (AQPs) that occur during pathogenesis, including conditions such as cancer, endometriosis, and arthritis. The ubiquitous function of AQPs in migration of diseased cells makes them a crucial target for potential therapeutics; this possibility has led to extensive research into the specific mechanisms underlying AQP-mediated diseased cell migration. The functions of AQPs depend on a diverse set of variables including cell type, AQP isoform, disease state, cell microenvironments, and even the subcellular localization of AQPs. To consolidate the considerable work that has been conducted across these numerous variables, here we summarize and review the last decade's research covering the role of AQPs in the migration and invasion of cells in diseased states.

Aquaporin-1 and Aquaporin-4 Expression in Ependyma, Choroid Plexus and Surrounding Transition Zones in the Human Brain.

The choroid plexus (CP) is a structure in the brain ventricles that produces the main part of the cerebrospinal fluid (CSF). It is covered with specialized cells which show epithelial characteristics and are the site of the blood-CSF barrier. These cells form a contiguous cell sheet with ventricle-lining ependymal cells which are known to express aquaporin-4 (AQP4). In contrast, CP epithelial cells express aquaporin-1 (AQP1) apically. We investigated the expression patterns of aquaporins in the CP-ependyma transition from human body donors using immunofluorescence and electron microscopy. Ependymal cells and subependymal astrocytes at the base of the CP showed a particularly high AQP4 immunoreactivity. Astrocytic processes formed a dense meshwork or glial plate around the blood vessels entering the CP. Interestingly, some of these astrocytic processes were in direct contact with the CP stroma, which contains fenestrated blood vessels, separated only by a basal lamina. Electron microscopy confirmed the continuity of the subastrocytic basal lamina with the CP epithelium. We also probed for components of the AQP4 anchoring dystrophin-dystroglycan complex. Immunolabeling for dystrophin and AQP4 showed an overlapping staining pattern in the glial plate but not in previously reported AQP4-positive CP epithelial cells. In contrast, dystroglycan expression was associated with laminin staining in the glial plate and the CP epithelium. This suggests different mechanisms for AQP4 anchoring in the cell membrane. The high AQP4 density in the connecting glial plate might facilitate the transport of water in and out of the CP stroma and could possibly serve as a drainage and clearing pathway for metabolites.

Astrocytes Transplanted during Early Postnatal Development Integrate, Mature, and Survive Long Term in Mouse Cortex.

Astrocytes have complex structural, molecular, and physiological properties and form specialized microenvironments that support circuit-specific functions in the CNS. To better understand how astrocytes acquire their unique features, we transplanted immature mouse cortical astrocytes into the developing cortex of male and female mice and assessed their integration, maturation, and survival. Within days, transplanted astrocytes developed morphologies and acquired territories and tiling behavior typical of cortical astrocytes. At 35-47 d post-transplantation, astrocytes appeared morphologically mature and expressed levels of EAAT2/GLT1 similar to nontransplanted astrocytes. Transplanted astrocytes also supported excitatory/inhibitory (E/I) presynaptic terminals within their territories, and displayed normal Ca2+ events. Transplanted astrocytes showed initially reduced expression of aquaporin 4 (AQP4) at endfeet and elevated expression of EAAT1/GLAST, with both proteins showing normalized expression by 110 d and one year post-transplantation, respectively. To understand how specific brain regions support astrocytic integration and maturation, we transplanted cortical astrocytes into the developing cerebellum. Cortical astrocytes interlaced with Bergmann glia (BG) in the cerebellar molecular layer to establish discrete territories. However, transplanted astrocytes retained many cortical astrocytic features including higher levels of EAAT2/GLT1, lower levels of EAAT1/GLAST, and the absence of expression of the AMPAR subunit GluA1. Collectively, our findings demonstrate that immature cortical astrocytes integrate, mature, and survive (more than one year) following transplantation and retain cortical astrocytic properties. Astrocytic transplantation can be useful for investigating cell-autonomous (intrinsic) and non-cell-autonomous (environmental) mechanisms contributing to astrocytic development/diversity, and for determining the optimal timing for transplanting astrocytes for cellular delivery or replacement in regenerative medicine.SIGNIFICANCE STATEMENT The mechanisms that enable astrocytes to acquire diverse molecular and structural properties remain to be better understood. In this study, we systematically analyzed the properties of cortical astrocytes following their transplantation to the early postnatal brain. We found that immature cortical astrocytes transplanted into cerebral cortex during early postnatal mouse development integrate and establish normal astrocytic properties, and show long-term survival in vivo (more than one year). In contrast, transplanted cortical astrocytes display reduced or altered ability to integrate into the more mature cerebral cortex or developing cerebellum, respectively. This study demonstrates the developmental potential of transplanted cortical astrocytes and provides an approach to tease apart cell-autonomous (intrinsic) and non-cell-autonomous (environmental) mechanisms that determine the structural, molecular, and physiological phenotype of astrocytes.

Aquaporin-5 Dynamic Regulation

Aquaporin-5 (AQP5), belonging to the aquaporins (AQPs) family of transmembrane water channels, facilitates osmotically driven water flux across biological membranes and the movement of hydrogen peroxide and CO2. Various mechanisms have been shown to dynamically regulate AQP5 expression, trafficking, and function. Besides fulfilling its primary water permeability function, AQP5 has been shown to regulate downstream effectors playing roles in various cellular processes. This review provides a comprehensive overview of the current knowledge of the upstream and downstream effectors of AQP5 to gain an in-depth understanding of the physiological and pathophysiological processes involving AQP5.

Assessing the Role of Aquaporin 4 in Skeletal Muscle Function.

Water transport across the biological membranes is mediated by aquaporins (AQPs). AQP4 and AQP1 are the predominantly expressed AQPs in the skeletal muscle. Since the discovery of AQP4, several studies have highlighted reduced AQP4 levels in Duchenne muscular dystrophy (DMD) patients and mouse models, and other neuromuscular disorders (NMDs) such as sarcoglycanopathies and dysferlinopathies. AQP4 loss is attributed to the destabilizing dystrophin-associated protein complex (DAPC) in DMD leading to compromised water permeability in the skeletal muscle fibers. However, AQP4 knockout (KO) mice appear phenotypically normal. AQP4 ablation does not impair physical activity in mice but limits them from achieving the performance demonstrated by wild-type mice. AQP1 levels were found to be upregulated in DMD models and are thought to compensate for AQP4 loss. Several groups investigated the expression of other AQPs in the skeletal muscle; however, these findings remain controversial. In this review, we summarize the role of AQP4 with respect to skeletal muscle function and findings in NMDs as well as the implications from a clinical perspective.

Importance of Water Transport in Mammalian Female Reproductive Tract.

Aquaporins (AQPs) are involved in water homeostasis in tissues and are ubiquitous in the reproductive tract. AQPs are classified into classical aquaporins (AQP0, 1, 2, 4, 5, 6 and 8), aquaglycerolporins (AQP3, 7, 9, and 10) and superaquaporins (AQP11 and 12). Nine AQPs were described in the mammalian female reproductive tract. Some of their functions are influenced by sexual steroid hormones. The continuous physiological changes that occur throughout the sexual cycle, pregnancy and parturition, modify the expression of AQPs, thus creating at every moment the required water homeostasis. AQPs in the ovary regulate follicular development and ovulation. In the vagina and the cervix, AQPs are involved mainly in lubrication. In the uterus, AQPs are mostly mediated by estradiol and progesterone to prepare the endometrium for possible embryo implantation and fetal development. In the placenta, AQPs are responsible for the fluid support to the fetus to maintain fetal homeostasis that ensures correct fetal development as pregnancy goes on. This review is focused on understanding the role of AQPs in the mammalian female reproductive tract during the sexual cycle of pregnancy and parturition.

Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes.

Prolonged inflammation and impaired re-epithelization are major contributing factors to chronic non-healing diabetic wounds; diabetes is also characterized by xerosis. Advanced glycation end products (AGEs), and the activation of toll-like receptors (TLRs), can trigger inflammatory responses. Aquaporin-3 (AQP3) plays essential roles in keratinocyte function and skin wound re-epithelialization/re-generation and hydration. Suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, mimics the increased acetylation observed in diabetes. We investigated the effects of TLR2/TLR4 activators and AGEs on keratinocyte AQP3 expression in the presence and absence of SAHA. Primary mouse keratinocytes were treated with or without TLR2 agonist Pam3Cys-Ser-(Lys)4 (PAM), TLR4 agonist lipopolysaccharide (LPS), or AGEs, with or without SAHA. We found that (1) PAM and LPS significantly upregulated AQP3 protein basally (without SAHA) and PAM downregulated AQP3 protein with SAHA; and (2) AGEs (100 µg/mL) increased AQP3 protein expression basally and decreased AQP3 levels with SAHA. PAM and AGEs produced similar changes in AQP3 expression, suggesting a common pathway or potential crosstalk between TLR2 and AGEs signaling. Our findings suggest that TLR2 activation and AGEs may be beneficial for wound healing and skin hydration under normal conditions via AQP3 upregulation, but that these pathways are likely deleterious in diabetes chronically through decreased AQP3 expression.

Hyperhidrosis: A Central Nervous Dysfunction of Sweat Secretion.

Hyperhidrosis (HH) is a central nervous dysfunction characterized by abnormally increased sweating due to a central dysregulation of sweat secretion. HH significantly affects the quality of life of patients in their private, social and professional environments. Physiologically, sweating is a mechanism that regulates body temperature, but it may also be triggered by emotional or gustatory stimuli. There are two main types of sweat glands: eccrine and apocrine glands. The central nervous system controls sweat secretion through the release of neurotransmitters into the autonomous nervous system (ANS) that activate the sweat glands. The hypothalamus has two separate neuronal pathways, one for thermoregulation and one for emotions. HH may thus be due to either a neuronal dysfunction of ANS regulation leading to a hyperactivity of the sympathetic nervous system, or to abnormal central processing of emotions. Crucially, there is no dysfunction of the sweat glands themselves. Various pathogenic mechanisms have been proposed to be involved in pathological sweat secretion in HH, ranging from structural changes within the ANS to increased expression of aquaporin 5 and upregulation of activin A receptor type 1 in eccrine sweat glands. Although a genetic predisposition has been demonstrated, it remains unclear exactly which genes are involved. To identify new, potential therapeutic targets and to improve treatment options, a good understanding of the signaling pathways involved, the underlying mechanisms, and the genetic components is essential. In this review we discuss the various aspects of sweat physiology and function that are necessary to explain pathological sweating. Our aim is to raise awareness of the complexity of HH to promote a better understanding of the disorder.