Expression Of AQP1 Research Articles

The cell polarity protein Scribble is downregulated by the water channel aquaporin-5 in breast cancer cells.

Breast carcinomas originate from cells in the terminal duct-lobular unit. Carcinomas are associated with increased cell proliferation and migration, altered cellular adhesion, as well as loss of epithelial polarity. In breast cancer, aberrant and high levels of AQP5 are associated with increased metastasis, poor prognosis and cancer recurrence. AQP5 increases proliferation and migration of cancer cells, and ectopic expression of AQP5 in normal epithelial cells reduces cell-cell adhesion and increases cell detachment and dissemination from migrating cell sheets, the latter via AQP5 mediated activation of the Ras pathway. Here, we investigated if AQP5 also affects cellular polarity by examining the relationship between the essential polarity protein Scribble and AQP5. In tissue samples from invasive lobular and ductal carcinomas, the majority of cells with high AQP5 expression displayed low Scribble levels, indicating an inverse relationship. Probing for interactions via a GST pull-down experiment revealed that AQP5 and Scribble interacted. Moreover, overexpression of AQP5 in the breast cancer cell line MCF7 reduced both size and circularity of 3D spheroids and induced cell detachment and dissemination from migrating cell sheets. In addition, Scribble levels were reduced. An AQP5 mutant cell line, that cannot activate Ras (AQP5S156A), displayed unchanged spheroid size and circularity and an intermediate level of Scribble, indicating that the effect of AQP5 on Scribble is, at least in part, dependent of AQP5 mediated activation of Ras. Thus, our results suggest that high AQP5 expression negatively regulates the essential polarity protein Scribble and thus, can affect cellular polarity in breast cancer.

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.

A mycorrhizal helper bacterium alleviates drought stress in mycorrhizal Helianthemum almeriense plants by regulating water relations and plant hormones

Complex interactions between mycorrhizal helper bacteria (MHBs) and mycorrhizal fungi have rarely been studied in the context of drought. Separately, both MHB inoculation and moderate drought stress have previously shown to enhance desert truffle mycorrhization in Helianthemum almeriense plants, but the combined effect of both of them has not been evaluated yet. The goal of this study is to determine whether mycorrhization between Helianthemum almeriense and the desert truffle Terfezia claveryi can be triggered by applying Pseudomonas mandelii #29 under drought stress and whether this could improve plant water-relations. To investigate this, we evaluated the effect of the combination of MHB inoculation with two different water regimes (well-watered and water-deficit) over the mycorrhizal development, root hydraulic properties, gene expression of AQPs and plant hormones. The results showed that presence of P. mandelii under drought stress caused a synergistic increase of fungal colonization and a higher nutrient uptake. Although drought stress decreased root hydraulic conductivity (Lpr) regardless of whether plants were MHB-inoculated or not, this decrease was buffered in MHB-inoculated plants, concomintantly with regulation of plant hormones, such as abscisic acid, and aquaporin gene expression. Our results indicate that drought-mediated tripartite interactions (P. mandelii #29 x T. claveryi x H. almeriense) are beneficial for the plant to cope with water stress.

β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus.

We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.

Single-cell RNA sequencing reveals changes in glioma-associated macrophage polarization and cellular states of malignant gliomas with high AQP4 expression

Glioma is the most common primary central nervous system tumor in adults. Aquaporin-4, as a water channel protein encoded by AQP4 in the brain, is reported to alter its aggregation status to affect plasma membrane dynamics and provide the potential for metastasis of tumor cells and components of the tumor microenvironment. We performed single-cell RNA transcriptome sequencing of 53059 cells from 13 malignant glioma samples and spotted that the expression of AQP4 differed between samples. The same result was observed in the TCGA glioma database, showing poor overall survival and poor response to chemotherapy in AQP4 overexpressed populations. Concomitant with the overexpression of AQP4, genes related to the immune system were also over-expressed, such as CD74, HES1, CALD1, and HEBP2, indicating AQP4 may relate to immune factors of tumor progression. We also found that tumor-associated macrophages tended to polarize toward M2 macrophages in the high AQP4 group. In glioblastoma samples, we examined cell status differences and identified that cell status differs according to AQP4 expression levels. Briefly, our study revealed substantial heterogeneity within malignant gliomas with different AQP4 expression levels, indicating the intricate connection between tumor cells and the tumor immune environment.

Aquaporin 5 in Alzheimer's disease: a link between oral and brain pathology?

Aquaporin 5 in Alzheimer's disease: a link between oral and brain pathology?

Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

Ablation of AQP5 gene in mice leads to olfactory dysfunction caused by hyposecretion of Bowman's gland.

Smell detection depends on nasal airflow, which can make absorption of odors to the olfactory epithelium by diffusion through the mucus layer. The odors then act on the chemo-sensitive epithelium of olfactory sensory neurons (OSNs). Therefore, any pathological changes in the olfactory area, for instance, dry nose caused by Sjögren's Syndrome (SS) may interfere with olfactory function. SS is an autoimmune disease in which aquaporin (AQP) 5 autoantibodies have been detected in the serum. However, the expression of AQP5 in olfactory mucosa and its function in olfaction is still unknown. Based on the study of the expression characteristics of AQP5 protein in the nasal mucosa, the olfaction dysfunction in AQP5 knockout (KO) mice was found by olfactory behavior analysis, which was accompanied by reduced secretion volume of Bowman's gland by using in vitro secretion measure system, and the change of acid mucin in nasal mucus layer was identified. By excluding the possibility that olfactory disturbance was caused by changes in OSNs, the result indicated that AQP5 contributes to olfactory functions by regulating the volume and composition of OE mucus layer, which is the medium for the dissolution of odor molecules. Our results indicate that AQP5 can affect the olfactory functions by regulating the water supply of BGs and the mucus layer upper the OE that can explain the olfactory loss in the patients of SS, and AQP5 KO mice might be used as an ideal model to study the olfactory dysfunction.

Cloning and Characterization of Aquaporins 11 and Its Expression Analysis under Molt Cycle in &lt;i&gt;Eriocheir sinensis&lt;/i&gt;

Aquaporins play important roles in water molecule transport, ion transport, and osmotic pressure regulation. In this study, the full-length cDNA of aquaporin from Chinese mitten crab ( Eirocheir sinensis ) was cloned for first time using reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends analyses. The&nbsp;full-length of AQP11 cDNA is 1746bp, with a 463bp 5&rsquo;-untranslated region (UTR), a&nbsp;476bp 3&rsquo;-UTR, and&nbsp;an open reading frame (ORF) of 807 bp which encodes a 269 amino acid polypeptide. The&nbsp;molecular mass of the predicted protein is 29.46 kDa with an estimated PI of 5.38. Bioinformatics software analysis revealed that AQP11 gene contains 4 transmembrane domains, 2 NPV structural units. Homologous analysis showed that AQP11 of Eirocheir sinensis &nbsp;has the highest homology to AQP11 of Litopenaeus vanname i . &nbsp;Real-time quantitative RT-PCR showed that AQP11 gene could be detected in all tested tissues of Eirocheir sinensis , with the highest expression level in intestine, followed by the brain, muscle and thoracic ganglion, and the lowest expression level in the hepatopancreas, gills and blood. In&nbsp;the&nbsp;intestinal, the expression of AQP11 was significantly lower at the&nbsp;intermolt stage (stages C) and premolt stage (stage D), significantly enhanced and reached the maximal level at the ecdysis stage (stage E).&nbsp;On&nbsp;the other hand, the expression of AQP11 gene in muscle showed low expression in the intermolt stage (stage C), and it was increased gradually at the premolt stage (stage D), significantly enhanced and reached the maximal level at the ecdysis stage (E stage), and then reaching the postmolt stage(AB stage) decline.&nbsp;In summary, our results indicate that AQP11 may play an important role in molting of Enirocheir sinensis.

Protective effect of selenium and vitamin C on the fertility of male rats given penconazole.

Penconazole is used in agriculture and human and veterinary medicine applications. It has been included in the acute toxicity hazard category by the WHO. This study examines the protective effect of selenium and vitamin C on the fertility of male rats given penconazole. Nine groups of rats were given penconazole at concentrations of 50 and 75 mg/ml and selenium and vitamin C at concentrations of 0.5 and 100 mg/ml, respectively. Serum levels of LH and FSH were measured with ELISA kits; β-actin, GPX4, AQP7, PRM2, and BAX gene expression was evaluated with real-time PCR performed on the left testis of each rat. LH, FSH, and testosterone levels were lower in the groups given penconazole (50 and 75 mg/kg). Histopathology showed that the groups given penconazole had the lowest number of spermatogonia and primary spermatocytes; these numbers were greater in the groups receiving penconazole together with selenium or vitamin C; and the highest counts were observed in separate groups given Se and vitamin C. GPX4, AQP7, PRM2 and BAX gene expression in the groups receiving penconazole was different from controls and was modulated by treatment with selenium or vitamin C. This study showed that antioxidant compounds have a strengthening effect on the reproductive system and can mitigate the destructive effects of chemical fungicides.

Amelioration of exosome and mesenchymal stem cells in rats infected with diabetic nephropathy by attenuating early markers and aquaporin-1 expression.

Diabetic nephropathy (DN) is a prevalent diabetic microvascular condition. It is the leading cause of kidney disease in the advanced stages. There is no currently effective treatment available. This research aimed to investigate the curative potentials of exosomes isolated from mesenchymal stem cells affecting DN. This study was performed on 70 male adult albino rats. Adult rats were randomized into seven groups: Group I: Negative control group, Group II: DN group, Group III: Balanites treated group, Group IV: MSCs treated group, Group V: Exosome treated group, Group VI: Balanites + MSCs treated group and Group VII: Balanites + exosome treated group. Following the trial period, blood and renal tissues were subjected to biochemical, gene expression analyses, and histopathological examinations. Results showed that MDA was substantially increased, whereas TAC was significantly decreased in the kidney in the DN group compared to normal health rats. Undesired elevated values of MDA levels and a decrease in TAC were substantially ameliorated in groups co-administered Balanites aegyptiacae with MSCs or exosomes compared to the DN group. A substantial elevation in TNF-α and substantially diminished concentration of IGF-1 were noticed in DN rats compared to normal health rats. Compared to the DN group, the co-administration of Balanites aegyptiacae with MSCs or exosomes substantially improved the undesirable elevated values of TNF-α and IGF-1. Furthermore, in the DN group, the mRNA expression of Vanin-1, Nephrin, and collagen IV was significantly higher than in normal healthy rats. Compared with DN rats, Vanin-1, Nephrin, and collagen IV Upregulation were substantially reduced in groups co-administered Balanites aegyptiacae with MSCs or exosomes. In DN rats, AQP1 expression was significantly lower than in normal healthy rats. Furthermore, the groups co-administered Balanites aegyptiacae with MSCs or exosomes demonstrated a substantial increase in AQP1 mRNA expression compared to DN rats.

Hepatic Aquaporin 10 Expression Is Downregulated by Activated NFκB Signaling in Human Obstructive Cholestasis.

Recent studies reported that the hepatic expression of AQP8 and AQP9 was downregulated in bile duct-ligated (BDL) rats and that overexpression of human AQP1 in the rat liver attenuated cholestasis. However, the hepatic expression of AQP10 and its regulatory mechanism in human cholestasis remain unclear. Serum and liver samples were collected from 34 patients with obstructive cholestasis and from 12 control patients. Eight-week-old male C57BL/6J mice were intravenously injected with an adeno-associated virus 8 (AAV8) encoding human AQP10 driven by a hepatocyte-specific Alb promotor (AAV8-Alb promotor-hAQP10) for functional studies. Constructs of the AQP10 promoter and PLC/PRF/5-ASBT cell lines were used for regulatory mechanism studies. AQP10 was significantly downregulated in patients with obstructive cholestasis and negatively associated with the serum levels of total bile acid (TBA). The hepatocyte-specific overexpression ofhAQP10significantly attenuated the cholestatic liver injury and intrahepatic bile acids (BA) accumulation in BDL mice. Conjugated BAs, such as TCA and inflammatory factor TNFα, significantly repressed AQP10 expression. Furthermore, NFκB p65/p50 directly bound to the AQP10 promotor and decreased its activity in PLC/RPF/5-ASBTcells and in the livers of patients with obstructive cholestasis. However, these changes were diminished by BAY 11-7082 (a specific inhibitor of NFκB signaling). We are the first to report that AQP10 was significantly decreased in patients with obstructive cholestasis. AQP10 overexpression significantly attenuated cholestatic liver injury in BDL mice. Therefore, overexpression of hAQP10 in the liver may be a valuable strategy for cholestasis intervention.

Recellularization of Acellular Xeno Kidney Scaffold: An In Vivo Method to Generate Bioartificial Kidney.

A significant hurdle for kidney tissue engineering is reproducing the complex three-dimensional structure of the kidney. In our study, a stepwise approach of generating a reproducible Xeno kidney scaffold from a goat kidney is described, which can be implanted and recellularized by host cells. We have proposed a combination of sodium dodecyl sulfate and Triton-X-100-based protocol to generate a reproducible Xeno kidney scaffold, which was then analyzed by histology, DNA quantification, SEM, and renal angiography. Further, a small portion from the cortico-medullar region of the acellular scaffold was implanted in the rat's kidney subcapsular pocket for a period of 1 month, to check the recruitment of host cells into the scaffold. Post implantation, the extracellular matrix of the scaffold was well preserved and it did not induce any damage or inflammation in the native kidney. Implantation of the Xeno scaffold resulted in apparent early vascularization which helped in the recruitment of the host cells, which was characterized by histology, immunohistochemistry, and scanning electron microscopy. Implanted Xeno scaffold showed AQP-1, Nephrin, α-SMA, and VEGF expression in proximal tubules and renal glomerulus. Importantly, Ki-67 and WTAP-expressing cells were also observed near proximal tubules suggesting a high level of proliferation in the scaffold. Thus, showing the potential of Xeno kidney development that can be recellularized by the host cell to engineer into a functional kidney.

Application of dredging fu-organs in cerebral edema after stroke

Stroke is one of the most common diseases in neurology, and the brain edema after stroke is an important factor affecting the prognosis of patients. It is particularly important to reduce the volume of brain edema in clinic. By studying the mechanism of Tongfu agent, it is shown that it can effectively reduce the water content of brain tissue by inhibiting the expression of AQP-4, reducing the permeability of blood-brain barrier and reducing the damage of inflammatory molecules, and it has achieved good curative effect in clinic, which is one of the common treatment methods for brain edema.

Aquaporins in Edema.

One of the most prevalent indications of water-electrolyte imbalance is edema. Aquaporins (AQPs) are a protein family that can function as water channels. Osmoregulation and body water homeostasis are dependent on the regulation of AQPs. Human kidneys contain nine AQPs, five of which have been demonstrated to have a role in body water balance: AQP1, AQP2, AQP3, AQP4, and AQP7. Water imbalance is connected with AQP dysfunction. Hyponatremia with elevated AQP levels can accompany edema, which can be caused by disorders with low effective circulating blood volume and systemic vasodilation, such as congestive heart failure (CHF), hepatic cirrhosis, or the syndrome of incorrect antidiuretic hormone secretion (SIADH). In CHF, upregulation of AQP2 expression and targeting is critical for water retention. AQP2 is also involved in aberrant water retention and the formation of ascites in cirrhosis of the liver. Furthermore, water retention and hyponatremia in SIADH are caused by increased expression of AQP2 in the collecting duct. Fluid restriction, demeclocycline, and vasopressin type-2 receptor antagonists are widely utilized to treat edema. The relationship between AQPs and edema is discussed in this chapter.

AQP4 mitigates chronic neuropathic pain-induced cognitive impairment in mice

Neuropathic pain is a risk factor for cognitive defects. The ubiquitous expression of AQP4 in astrocytes throughout the central nervous system is altered in the neurodegenerative disease. However, the exact role of AQP4 in cognitive impairment induced by chronic neuropathic pain remains unclear. In this study, we discovered that AQP4 protein and mRNA expression decreased time-dependently in the model of chronic neuropathic pain-induced cognitive disorder. AQP4 overexpression recovered mice from cognitive impairment. Furthermore, the concentration of Aβ1–42 in the serum and hippocampus reduced in mice with AQP4 overexpression adeno-associated virus injection. In conclusion, AQP4 in astrocytes is important in mitigating cognitive impairment caused by chronic neuropathic pain.

Therapeutic effects of Bombax ceiba flower aqueous extracts against loperamide-induced constipation in mice

Context Bombax ceiba Linnaeus (Bombacaceae) is known as silk cotton tree, the flowers of which are used in many medicinal applications. Objective To investigate the therapeutic effect of B. ceiba flower aqueous extracts (BCE) against loperamide-induced constipation and characterize the chemical composition of BCE. Materials and methods Sixty male Kunming mice were divided into control (saline), model (10 mg/kg loperamide + saline), phenolphthalein (10 mg/kg loperamide + 10 mg/kg phenolphthalein) and different dosage of BCE (10 mg/kg loperamide + 40, 80 and 160 mg/kg BCE, respectively) groups, and received intragastric administrations for eight days. Faecal water content, number of faeces, first black-stool defecation time and gastrointestinal transit rates were evaluated. Various biochemical and molecular biomarkers were assessed in blood and colon. UPLC-ESI-QTOF-MS/MS was used to tentatively identify the composition of the BCE. Results BCE treatment (160 mg/kg) could increase faecal water (15.75%), faeces number (11.65%), gastrointestinal transit rate (25.37%) and decrease first black-stool defecation time (24.04%). The BCE (80 mg/kg) increased the serum level of motilin (30.62%), gastrin (54.46%) and substance P (18.99%), and decreased somatostatin (19.47%). Additionally, the BCE (160 mg/kg) reduced the mucosal damage, restored colonic goblet cell function, down-regulated the protein expression of AQP3 (33.60%) and increased c-kit protein expression (11.63%). Twelve known compounds, including protocatechuic acid, chlorogenic acid and rutin, previously reported in B. ceiba, were identified in the BCE. Discussion and conclusions This study suggested that BCE is a promising agent for the treatment of constipation.

The Critical Biomarkers Identification of Insulin Signaling Involved in Initiating cAMP Signaling Mediated Salivary Secretion in Sjogren Syndrome: Transcriptome Sequencing in NOD Mice Model

BackgroundSjogren’s syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood.MethodsIn this study, we used NOD mice model to monitor changes in mice’s salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes.ResultsWe found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion.ConclusionThe new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting.

Daidzein Protects Caco-2 Cells against Lipopolysaccharide-Induced Intestinal Epithelial Barrier Injury by Suppressing PI3K/AKT and P38 Pathways.

The intestinal epithelium provides an important barrier against bacterial endotoxin translocation, which can regulate the absorption of water and ions. The disruption of epithelial barrier function can result in water transport and tight junction damage, or further cause diarrhea. Therefore, reducing intestinal epithelial barrier injury plays an important role in diarrhea. Inflammatory response is an important cause of intestinal barrier defects. Daidzein improving the barrier integrity has been reported, but the effect on tight junction proteins and aquaporins is not well-described yet, and the underlying mechanism remains indistinct in the human intestinal epithelium. This study aimed to investigate the effects and mechanisms of daidzein on intestinal epithelial barrier injury induced by LPS, and a barrier injury model induced by LPS was established with human colorectal epithelial adenocarcinoma cell line Caco-2 cells. We found that daidzein protected the integrity of Caco-2 cell monolayers, reversed LPS-induced downregulation of ZO-1, occludin, claudin-1, and AQP3 expression, maintained intercellular junction of ZO-1, and suppressed NF-κB and the expression of inflammatory factors (TNF-α, IL-6). Furthermore, we found that daidzein suppressed the phosphorylation of the PI3K/AKT and P38 pathway-related proteins and the level of the related genes, and the PI3K/AKT and P38 pathway inhibitors increased ZO-1, occludin, claudin-1, and AQP3 expression. The study showed that daidzein could resist LPS-induced intestinal epithelial barrier injury, and the mechanism is related to suppressing the PI3K/AKT and P38 pathways. Therefore, daidzein could be a candidate as a dietary supplementation or drug to prevent or cure diarrhea.

Fasting influences aquaporin expression, water transport and adipocyte metabolism in the peritoneal membrane.

The water channels aquaporin-1 (AQP1) and AQP7 are abundantly expressed in the peritoneal membrane. While AQP1 facilitates water transport during peritoneal dialysis (PD), the role of AQP7, which mediates glycerol transport during fasting, remains unknown. We investigated the distribution of AQP7 and AQP1 and used a mouse model of PD to investigate the role of AQP7 in the peritoneal membrane at baseline and after fasting. Single nucleus RNA-sequencing revealed that AQP7 was mostly detected in mature adipocytes, whereas AQP1 was essentially expressed in endothelial cells. Fasting induced significant decreases in whole body fat, plasma glucose, insulin and triglycerides, as well as higher plasma glycerol and corticosterone levels in mice, paralleled by major decreases in adipocyte size and levels of fatty acid synthase and leptin, and increased levels of hormone-sensitive lipase mRNAs in the peritoneum. Mechanistically, fasting upregulated the expression of AQP1 and AQP7 in the peritoneum, with increased ultrafiltration but no change in small solute transport. Studies based on Aqp1 and Aqp7 knockout mice and RU-486 inhibition demonstrated that the glucocorticoid induction of AQP1 mediates the increase in ultrafiltration whereas AQP7 regulates the size of adipocytes in the peritoneum. Fasting induces a coordinated regulation of lipolytic and lipogenic factors and aqua(glycero)porins in the peritoneum, driving structural and functional changes. These data yield novel information on the specific roles of aquaporins in the peritoneal membrane and indicate that fasting improves fluid removal in a mouse model of PD.