Characterization of SIPs-type aquaporins and their roles in response to environmental cues in rice (Oryza sativa L.).

BACKGROUND: Aquaporins (AQPs) facilitate water diffusion across biological membranes and are involved in all phases of growth and development. Small and basic intrinsic proteins (SIPs) belong to the fourth subfamily of the plant AQPs. Although SIPs are widely present in higher plants, reports on SIPs are limited. Rice is one of the major food crops in the world, and water use is an important factor affecting rice growth and development; therefore, this study aimed to provide information relevant to the function and environmental response of the rice SIP gene family. RESULTS: The rice (Oryza sativa L. japonica) genome encodes two SIP-like genes, OsSIP1 and OsSIP2, whose products are predominantly located in the endoplasmic reticulum (ER) membrane but transient localization to the plasma membrane is not excluded. Heterologous expression in a yeast aquaglyceroporin-mutant fps1Δ showed that both OsSIP1 and OsSIP2 made the cell more sensitive to KCl, sorbitol and H2O2, indicating facilitated permeation of water and hydrogen peroxide. In addition, the yeast cells expressing OsSIP2 were unable to efflux the toxic methylamine taken up by the endogenous MEP permeases, but OsSIP1 showed subtle permeability to methylamine, suggesting that OsSIP1 may have a wider conducting pore than OsSIP2. Expression profiling in different rice tissues or organs revealed that OsSIP1 was expressed in all tissues tested, whereas OsSIP2 was preferentially expressed in anthers and weakly expressed in other tissues. Consistent with this, histochemical staining of tissues expressing the promoter-ß-glucuronidase fusion genes revealed their tissue-specific expression profile. In rice seedlings, both OsSIPs were upregulated to varied levels under different stress conditions, including osmotic shock, high salinity, unfavorable temperature, redox challenge and pathogen attack, as well as by hormonal treatments such as GA, ABA, MeJA, SA. However, a reduced expression of both OsSIPs was observed under dehydration treatment. CONCLUSIONS: Our results suggest that SIP-like aquaporins are not restricted to the ER membrane and are likely to be involved in unique membrane functions in substrate transport, growth and development, and environmental response.

Mechanistic complement of autosomal dominant polycystic kidney disease: the role of aquaporins.

Autosomal dominant polycystic kidney disease is a genetic kidney disease caused by mutations in the genes PKD1 or PKD2. Its course is characterized by the formation of progressively enlarged cysts in the renal tubules bilaterally. The basic genetic explanation for autosomal dominant polycystic kidney disease is the double-hit theory, and many of its mechanistic issues can be explained by the cilia doctrine. However, the precise molecular mechanisms underpinning this condition's occurrence are still not completely understood. Experimental evidence suggests that aquaporins, a class of transmembrane channel proteins, including aquaporin-1, aquaporin-2, aquaporin-3, and aquaporin-11, are involved in the mechanism of autosomal dominant polycystic kidney disease. Aquaporins are either a potential new target for the treatment of autosomal dominant polycystic kidney disease, and further study into the physiopathological role of aquaporins in autosomal dominant polycystic kidney disease will assist to clarify the disease's pathophysiology and increase the pool of potential treatment options. We primarily cover pertinent findings on aquaporins in autosomal dominant polycystic kidney disease in this review.

Effects of Zinc Combined with Metformin on Zinc Homeostasis, Blood-Epididymal Barrier, and Epididymal Absorption in Male Diabetic Mice.

Diabetes increases the likelihood of germ cell damage, hypogonadism, and male infertility. Diabetes leads to lower zinc (Zn) levels, an important micronutrient for maintaining male fertility, and zinc deficiency can lead to decreased male fertility through multiple mechanisms. The aim of this study was to investigate the effect of combined metformin and zinc administration on epididymis in diabetic mice; 10 of 50 male mice were randomly selected as the control group (group C), and the remaining 40 mice were randomly divided into untreated diabetes group (group D), diabetes + zinc group (group Z), diabetes + metformin group (group M), and diabetes + metformin + zinc group (group ZM) with 10 mice each. Diabetic mice in group Z received oral zinc (10 mg/kg) once daily for 4 weeks; diabetic mice in group M received oral metformin (200 mg/kg) once daily for 4 weeks; diabetic mice in group ZM received oral metformin and zinc once daily for 4 weeks; and groups C and D received the same amount of sterile water by gavage. Overnight fasted mice were sacrificed, and blood samples, mouse epididymides, and sperm were collected for further experiments. In group D, fasting blood glucose and insulin resistance index increased significantly, semen quality, serum insulin, and testosterone decreased, and epididymal structure was disordered. In group D, epididymal tissue zinc, free zinc ions in the caput, and cauda of epididymis and zinc transporter (ZnT2) decreased significantly, while ZIP12, metallothionein (MT), and metal transcription factor (MTF1) increased significantly. In addition, the expressions of blood-epididymal barrier (BEB)-related molecules (including ZO-1 ß-catenin and N-cadherin) and aquaporins (AQPs, including AQP3, AQP9, and AQP11) in the epididymis of mice in group D were significantly decreased. In addition, compared with groups D, Z, and M, in the ZM group, the expression of BEB-related molecules (including ZO-1, ß-catenin, and N-cadherin) and aquaporins (AQP3, AQP9, and AQP11) in epididymis tissue were significantly increased, and sperm motility and serum testosterone were significantly increased. It was concluded that male diabetic mice have a disturbed epididymal structure and decreased semen quality by causing an imbalance in epididymal zinc homeostasis, BEB, and impaired absorptive function. The combination of zinc and metformin is an effective and safe alternative treatment and provides additional benefits over metformin alone.

Homeostatic status of thyroid hormones and brain water movement as determinant factors in biology of cerebral gliomas: a pilot study using a bioinformatics approach.

Introduction: The expression and localization of the water channel transporters, aquaporins (AQPs), in the brain are substantially modified in gliomas during tumorigenesis, cell migration, edema formation, and resolution. We hypothesized that the molecular changes associated with AQP1 and AQP4 in the brain may potentially be anticancer therapeutic targets. To test this hypothesis, a bioinformatics analysis of publicly available data from international consortia was performed. Methods: We used RNA-seq as an experimental strategy and identified the number of differential AQP1 and AQP4 transcript expressions in glioma tissue compared to normal brain tissue. Results: AQPs genes are overexpressed in patients with glioma. Among the glioma subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low-grade glioma) and classical (high-grade glioma). Overall survival analysis demonstrated that both AQP genes can be used as prognostic factors for patients with low-grade glioma. Additionally, we observed a correlation between the expression of genes involved in the tyrosine and thyroid hormone pathways and AQPs, namely: PNMT, ALDH1A3, AOC2, HGDATP1B1, ADCY5, PLCB4, ITPR1, ATP1A3, LRP2, HDAC1, MED24, MTOR, and ACTB1 (Spearman's coefficient = geq 0.20 and p-value = ≤ 0.05). Conclusion: Our findings indicate that the thyroid hormone pathways and AQPs 1 and 4 are potential targets for new anti-tumor drugs and therapeutic biomarkers for malignant gliomas.

Transcriptomics-based analysis reveals the nephrotoxic effects of triphenyltin (TPT) on SD rats by affecting RAS, AQPs and lipid metabolism.

Triphenyltin (TPT) is a class of organotin compounds that are extensively used in industry and agriculture. They have endocrine-disrupting effects and cause severe environmental contamination. Pollutants may accumulate in the kidneys and cause pathological complications. However, the mechanism of TPT's toxicological effects on the kidney remains unclear. This study aimed to investigate the toxic effects and mechanism of action of TPT exposure on renal impairment in rats. Male SD rats were divided into four groups: the Ctrl group (control group), TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 28 days of exposure to TPT, we observed the morphology and structure of kidney tissue using HE, PASM, and Masson staining. We also detected serum biochemical indexes, performed transcriptome sequencing of rat kidney tissue using RNA-seq. Furthermore, protein expression levels were measured through immunohistochemistry and gene expression levels were determined using RT-qPCR. The study results indicated a decrease in kidney weight and relative kidney weight after 28 days of exposure to TPT. Additionally, TPT caused damage to kidney structure and function, as evidenced by HE staining, PASM staining, and serum biochemical tests. Transcriptomics identified 352 DEGs, and enrichment analyses revealed that TPT exposure primarily impacted the renin-angiotensin system (RAS). The expression levels of water channel proteins were reduced, and the expression levels of RAS and lipid metabolism-related genes (Mme, Ace, Fasn, Cyp4a8, Cpt1b and Ppard) were significantly decreased in the TPT-treated group. In summary, exposure to TPT may impair renal structure and function in rats by affecting RAS, AQPs, and lipid metabolism.

Verification of the gene and protein expression of the aquaglyceroporin AQP3 in the mammalian lens.

Transport of water is critical for maintaining the transparency of the avascular lens, and the lens is known to express at least five distinctly different water channels from the Aquaporin (AQP) family of proteins. In this study we report on the identification of a sixth lens AQP, AQP3 an aquaglyceroporin, which in addition to water also transports glycerol and H2O2. AQP3 was identified at the transcript level and protein levels using RT-PCR and Western blotting, respectively, in the mouse, rat, bovine and human lens, showing that its expression is conserved in the mammalian lens. Western blotting showed AQP3 in the lens exists as 25 kDa non-glycosylated and 37 kDa glycosylated monomeric forms in all lens species. To identify the regions in the lens where AQP3 is expressed Western blotting was repeated using epithelial, outer cortical and inner cortical/core fractions isolated from the mouse lens. AQP3 was found in all lens regions, with the highest signal of non-glycosylated AQP3 being found in the epithelium. While in the inner cortex/core region AQP3 signal was not only lower but was predominately from the glycosylated form of AQP3. Immunolabelling of lens sections with AQP3 antibodies confirmed that AQP3 is found in all regions of the adult mouse, and also revealed that the subcellular distribution of AQP3 changes as a function of fiber cell differentiation. In epithelial and peripheral fiber cells of the outer cortex AQP3 labelling was predominately associated with membrane vesicles in the cytoplasm, but in the deeper regions of the lens AQP3 labelling was associated with the plasma membranes of fiber cells located in the inner cortex and core of the lens. To determine how this adult pattern of AQP3 subcellular distribution was established, immunolabelling for AQP3 was performed on embryonic and postnatal lenses. AQP3 expression was first detected on embryonic day (E) 11 in the membranes of primary fiber cells that have started to elongate and fill the lumen of the lens vesicle, while later at E16 the AQP3 labelling in the primary fiber cells had shifted to a predominately cytoplasmic location. In the following postnatal (P) stages of lens growth at P3 and P6, AQP3 labelling remained cytoplasmic across all regions of the lens and it was not until P15 when the pattern of localisation of AQP3 changed to an adult distribution with cytoplasmic labelling detected in the outer cortex and membrane localisation detected in the inner cortex and core of the lens. Comparison of the AQP3 labelling pattern to those obtained previously for AQP0 and AQP5 showed that the subcellular distribution was more similar to AQP5 than AQP0, but there were still significant differences that suggest AQP3 may have unique roles in the maintenance of lens transparency.

Classical famous prescription of Jichuan decoction improved loperamide-induced slow transit constipation in rats through the cAMP/PKA/AQPs signaling pathway and maintained inflammatory/intestinal flora homeostasis.

Introduction: Jichuan decoction (JCD) is a well-known traditional Chinese medicinal formula that moistens the intestines and is widely used for the treatment of constipation in China. However, its effects and mechanisms in alleviating slow transit constipation (STC) in vivo remain unclear. We attempted to demonstrate the effect of JCD, with and without essential oil (VO), on intestinal transit and its underlying molecular mechanisms in rats with loperamide-induced STC. Materials and methods: Water consumption, body weight, fecal water content, time to first melena excretion, and intestinal transit ratio of the animals were measured. 5-Hydroxytryptamine (5-HT), substance P (SP), vasoactive intestinal peptide (VIP), and interleukin-6 (IL-6) levels in the sera of rats were evaluated using ELISA. Hematoxylin and eosin and Periodic Acid-Schiff staining were used to determine intestinal tissue histology, while quantitative real-time PCR, western blotting, and immunohistochemical analysis were used to assess the relative expression levels of cAMP/PKA/AQPs pathway- and inflammation-related proteins. 16 S rDNA sequence analysis of rat feces was used to determine the diversity and abundance of the intestinal flora. Results: The JCD groups showed reduced time to first melena excretion and expression of VIP and IL-6. The JCD groups, specifically JCD + VO groups, showed increased fecal water content, intestinal transit rate, and SP expression. Further, these groups showed improved histological characteristics of the colon, with no significant change in the index of immune organs or morphological characteristics of other organs. In addition, a significant decrease in the activation of the cAMP/PKA/AQPs signaling pathway in the colon tissue was observed in these groups, specifically the JCD + VO groups. Moreover, treatment with JCD, with or without VO, downregulated the expression of inflammatory factors and enriched the diversity of intestinal flora as evidenced by polymorphism analysis and the contents of Bacteroides, Lactobacillus, and Erysipelas, with the JCD + VO groups showing better therapeutic outcomes. Conclusion: JCD improved loperamide-induced STC, and co-administration with VO exhibited better activity than sole JCD therapy. JCD may improve STC by inhibiting the cAMP/PKA/AQPs signaling pathway and maintaining inflammatory/intestinal flora homeostasis.

Genome-wide identification of Avicennia marina aquaporins reveals their role in adaptation to intertidal habitats and their relevance to salt secretion and vivipary.

Aquaporins (AQPs) regulate the transport of water and other substrates, aiding plants in adapting to stressful environments. However, the knowledge of AQPs in salt-secreting and viviparous Avicennia marina is limited. In this study, 46 AmAQPs were identified in A. marina genome, and their subcellular localisation and function in transporting H2 O2 and boron were assessed through bioinformatics analysis and yeast transformation. Through analysing their expression patterns via RNAseq and real-time quantitative polymerase chain reaction, we found that most AmAQPs were downregulated in response to salt and tidal flooding. AmPIP (1;1, 1;7, 2;8, 2;9) and AmTIP (1;5, 1;6) as salt-tolerant candidate genes may contribute to salt secretion together with Na+ /H+ antiporters. AmPIP2;1 and AmTIP1;5 were upregulated during tidal flooding and may be regulated by anaerobic-responsive element and ethylene-responsive element cis-elements, aiding in adaptation to tidal inundation. Additionally, we found that the loss of the seed desiccation and dormancy-related TIP3 gene, and the loss of the seed dormancy regulator DOG1 gene, or DOG1 protein lack heme-binding capacity, may be genetic factors contributing to vivipary. Our findings shed light on the role of AQPs in A. marina adaptation to intertidal environments and their relevance to salt secretion and vivipary.

Stool-softening effect and action mechanism of free anthraquinones extracted from Rheum palmatum L. on water deficit-induced constipation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined. AIM OF THE STUDY: The current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats. MATERIALS AND METHODS: A rat model of water deficit-induced constipation was established to induce constipation, and these rats were treated with RhA and its monomers. ELISA, histopathology, immunohistochemistry, qPCR and Western blotting based on network pharmacology and molecular docking were conducted to explore the possible mechanism of action of RhA and its monomers. RESULTS: RhA, aloe-emodin, rhein, and chrysophanol showed stool-softening activity, and the combination of aloe-emodin and rhein had the strongest softening effect on faecal pellets. Aloe-emodin, rhein, and chrysophanol significantly increased the serum levels of vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP), upregulated the expression of VIP, cyclase-associated protein 1 (CAP1), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3), aquaporin 4 (AQP4), and aquaporin 8 (AQP8), decreased the expression of epithelial sodium channel (ENaC) and Na+/H+ exchanger 3 (NHE3), and reduced the colonic tissue concentration of Na+-K+-ATPase in the constipated rats. Osmolality of colonic fluid in model rats treated by RhA, aloe-emodin, rhein, and chrysophanol was increased. CONCLUSION: Aloe-emodin, rhein, and chrysophanol were the stool-softening components of the RhA extract, and there were certain drug-interactions between the components. RhA upregulated VIP expression, activated the cyclic adenosine monophosphate protein kinase A (cAMP/PKA) pathway, and further stimulated CFTR expression while inhibiting NHE3 and ENaC expression, resulting in a hypertonic state in the colonic lumen. Water transport could then be driven by an osmotic gradient, which in turn led to the upregulation of AQP3, AQP4, and AQP8 expression. In addition, RhA likely improved gastrointestinal motility by increasing serum VIP, SP, and MTL concentrations, thus promoting faecal excretion.

Effects of a high-salt diet on MAP and expression levels of renal ENaCs and aquaporins in SHR.

An increase in blood pressure by a high-salt (HS) diet may change the expression levels of renal epithelial sodium channels (ENaCs) and aquaporins (AQPs). Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were exposed to HS and regular-salt (RS) diets for 6 weeks. Mean arterial pressure (MAP) and plasma atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone, and arginine vasopressin (AVP) levels were determined. Expression of mRNA levels of ENaCs and AQPs were quantified by real-time PCR. The MAP was higher in SHRs on the HS diet. Plasma Ang II and aldosterone levels were low while plasma ANP level was high in both strains of rats. Renal expression of mRNA levels of α-, ß-, and γ-ENaCs was lowered in SHRs on the HS diet. Meanwhile, renal AQP1, AQP2, and AQP7 mRNA expression levels were lowered in both strains of rats on the HS diet. Suppression of mRNA expression levels of ENaC and AQP subunits suggests that the high-salt-induced increase in the MAP of SHR may not be solely due to renal sodium and water retention.

Kidney morphology and renal expression of aquaporins 2, 3 and 4 during cerulein - Induced chronic pancreatitis in pigs.

PURPOSE: Chronic pancreatitis (CP) is associated with serious complications and reduced quality of life. Kidney failure is a frequent complication of acute pancreatitis (AP), however limited information is available regarding the impact of CP on this condition. In the kidney, 9 aquaporins (AQPs) are expressed to maintain body water homeostasis and concentrate urine. The purpose of this study was to morphologically assess and analyze the location and expression of AQP2, AQP3 and AQP4 and determine whether CP affects renal structure and expression of AQPs in collecting duct (CD) principal cells. MATERIALS/METHODS: CP was induced in domestic pigs through intramuscular injections of cerulein (1 â€‹µg/kg â€‹bw/day for 6 days; n â€‹= â€‹5); pigs without CP (n â€‹= â€‹5) were used as a control group. Kidney samples were collected 6 weeks after the last injection and subjected to histological examination. Expression of AQPs was determined by immunohistochemistry and Western blot. RESULTS: The kidneys of animals with CP exhibited moderate changes, including glomerular enlargement, increased collagen percentage, numerous stromal erythrorrhages and inflammatory infiltrations compared to control group. Although the total abundance of AQP2 in the CD decreased in pigs after cerulein administration, the difference was not statistically significant. Expression of AQP3 and AQP4 was limited to the basolateral membrane of the CD cells. AQP4 abundance remained relatively stable in both groups, while AQP3 expression increased nearly three-fold in pigs with CP. CONCLUSION: This study identified morphological alterations and a statistically significant increase in the expression of renal AQP3 when pigs developed CP.

Potential Role of Antibodies against Aquaporin-1 in Patients with Central Nervous System Demyelination.

Aquaporins (AQPs; AQP0-AQP12) are water channels expressed in many and diverse cell types, participating in various functions of cells, tissues, and systems, including the central nervous system (CNS). AQP dysfunction and autoimmunity to AQPs are implicated in several diseases. The best-known example of autoimmunity against AQPs concerns the antibodies to AQP4 which are involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathy, causing also CNS demyelination. The present review focuses on the discovery and the potential role of antibodies against AQP1 in the CNS, and their potential involvement in the pathophysiology of NMOSD. We describe (a) the several techniques developed for the detection of the AQP1-antibodies, with emphasis on methods that specifically identify antibodies targeting the extracellular domain of AQP1, i.e., those of potential pathogenic role, and (b) the available evidence supporting the pathogenic relevance of AQP1-antibodies in the NMOSD phenotype.

Genome-Wide Identification of Aqp Family Related to Spermatogenesis in Turbot (Scophthalmus maximus).

The development and maturation of sperm entails intricate metabolic processes involving water molecules, amino acids, hormones, and various substances. Among these processes, the role of aquaporins (aqps) in the testis is crucial. Turbot (Scophthalmus maximus) is a significant marine flatfish species in China; however, natural egg laying in females is not feasible under cultured conditions. Consequently, artificial insemination becomes necessary, requiring the retrieval of sperm and eggs through artificial methods. In this study, we combined genomic, transcriptomics, RT-qPCR, computer-assisted sperm analysis (CASA), and immunohistochemistry to investigate the involvement of the aqp family in spermatogenesis in turbot. Through genomic data analysis, we identified 16 aqps genes dispersed across 13 chromosomes, each exhibiting the characteristic major intrinsic protein (MIP) domain associated with AQPs. The results from RNA-seq and RT-qPCR analysis revealed prominent expression of aqp4, 10, and 12 during the proliferative stage, whereas aqp1 showed primary expression during the mature stage. aqp11 displayed high expression levels during both MSII and MSV stages, potentially contributing significantly to the proliferation and maturation of male germ cells. Conversely, aqp8 showed elevated expression levels during the MSIII, MSIII-IV, and MSIV stages, suggesting its direct involvement in spermiogenesis. Immunohistochemical analysis unveiled the predominant localization of AQP1 protein in male germ cells rather than Sertoli cells, specifically concentrated in the head of sperm within cysts. Furthermore, a noteworthy decline in sperm motility was observed when sperm were subjected to treatment with either the AQP1-specific inhibitor (HgCl2) or the AQP1 antibody. However, no direct correlation was found between the expression of Smaqp1 and sperm quality. Overall, these findings provide new insights into the involvement of aqps in teleost spermatogenesis. Moreover, they hold potential for improving techniques related to sperm activation and cryopreservation, offering valuable knowledge for future advancements in this field.

The emerging science of Glioception: Contribution of glia in sensing, transduction, circuit integration of interoception.

Interoception is the process by which the nervous system regulates internal functions to achieve homeostasis. The role of neurons in interoception has received considerable recent attention, but glial cells also contribute. Glial cells can sense and transduce signals including osmotic, chemical, and mechanical status of extracellular milieu. Their ability to dynamically communicate "listening" and "talking" to neurons is necessary to monitor and regulate homeostasis and information integration in the nervous system. This review introduces the concept of "Glioception" and focuses on the process by which glial cells sense, interpret and integrate information about the inner state of the organism. Glial cells are ideally positioned to act as sensors and integrators of diverse interoceptive signals and can trigger regulatory responses via modulation of the activity of neuronal networks, both in physiological and pathological conditions. We believe that understanding and manipulating glioceptive processes and underlying molecular mechanisms provide a key path to develop new therapies for the prevention and alleviation of devastating interoceptive dysfunctions, among which pain is emphasized here with more focused details.

Morphological Effects of Cigarette Smoking on Respiratory System and Related Functions Based on AQPs Expression

SUMMARY: A great deal of attention of air pollution on respiratory health is increasing, particularly in relation to haze days. It is that exposure to cigarette smoke augments the toxicity of common air contaminants, thereby increasing the complexity of respiratory diseases. Although there are various mechanisms involved to respiratory diseases caused or worsen by cigarette smoking, in which the role of AQPs in the lung with regard to fluid homeostasis still remains elusive. In this paper, we copied the rat models based on smoke generator, and investigated the morphological changes of mucosa and related functions depending on the balance of lining liquid of alveoli via AQPs expression. Compared with normal group, weak labelling of AQP1 and AQP5 protein abundance were clearly detected in the corresponding part of smoke exposure groups compared with normal group. Hence, it is suggested that the contribution of AQPs in the lung is diminished, thereby causing perturbed balancing between resorptive and secretory fluid homeostasis under cigarette smoking.

Cada vez se presta más atención a la contaminación del aire en la salud respiratoria, particularmente, en relación con los días de neblina. En consecuencia la exposición al humo del cigarrillo aumenta la toxicidad de los contaminantes comunes del aire, lo que además aumenta la complejidad de las enfermedades respiratorias. Aunque existen varios mecanismos involucrados en las enfermedades respiratorias causadas o empeoradas por el tabaquismo, en las que el papel de las AQP en el pulmón respecto a la homeostasis de líquidos sigue siendo difícil de alcanzar. En este artículo, copiamos los modelos de rata basados en el generador de humo e investigamos los cambios morfológicos de la mucosa y las funciones relacionadas según el equilibrio del líquido de revestimiento de los alvéolos a través de la expresión de AQP. En comparación con el grupo normal, se detectó claramente un etiquetado débil de la abundancia de proteínas AQP1 y AQP5 en la parte correspondiente de los grupos de exposición al humo en comparación con el grupo control. Por lo tanto, se sugiere que la contribución de las AQP en el pulmón está disminuida, provocando así un equilibrio perturbado entre la homeostasis del líquido secretor y de reabsorción bajo el hábito de fumar cigarrillos.

Aquaporins and Ion Channels as Dual Targets in the Design of Novel Glioblastoma Therapeutics to Limit Invasiveness.

Current therapies for Glioblastoma multiforme (GBM) focus on eradicating primary tumors using radiotherapy, chemotherapy and surgical resection, but have limited success in controlling the invasive spread of glioma cells into a healthy brain, the major factor driving short survival times for patients post-diagnosis. Transcriptomic analyses of GBM biopsies reveal clusters of membrane signaling proteins that in combination serve as robust prognostic indicators, including aquaporins and ion channels, which are upregulated in GBM and implicated in enhanced glioblastoma motility. Accumulating evidence supports our proposal that the concurrent pharmacological targeting of selected subclasses of aquaporins and ion channels could impede glioblastoma invasiveness by impairing key cellular motility pathways. Optimal sets of channels to be selected as targets for combined therapies could be tailored to the GBM cancer subtype, taking advantage of differences in patterns of expression between channels that are characteristic of GBM subtypes, as well as distinguishing them from non-cancerous brain cells such as neurons and glia. Focusing agents on a unique channel fingerprint in GBM would further allow combined agents to be administered at near threshold doses, potentially reducing off-target toxicity. Adjunct therapies which confine GBM tumors to their primary sites during clinical treatments would offer profound advantages for treatment efficacy.

Transport Characteristics of Aquaporins.

Aquaporins (AQP) are a class of the integral membrane proteins. The main physiological function of AQPs is to facilitate the water transport across plasma membrane of cells. However, the transport of various kinds of small molecules by AQPs is an interesting topic. Studies using in vitro cell models have found that AQPs mediated transport of small molecules, including glycerol, urea, carbamides, polyols, purines, pyrimidines and monocarboxylates, and gases such as CO2, NO, NH3, H2O2 and O2, although the high intrinsic membrane permeabilities for these gases make aquaporin-facilitated transport not dominant in physiological mechanism. AQPs are also considered to transport silicon, antimonite, arsenite and some ions; however, most data about transport characteristics of AQPs are derived from in vitro experiments. The physiological significance of AQPs that are permeable to various small molecules is necessary to be determined by in vivo experiments. This chapter will provide information about the transport characteristics of AQPs.

mRNA Expression of Aquaporins in Human Luteinized Granulosa Cells from Different Diameter Follicles / 中山大学学报(医学科学版)

ObjectiveTo investigate the mRNA expression levels of various aquaporins （AQPs） in luteinized granulosa cells from follicles of different diameters. MethodsFrom March 25， 2022 to September 23， 2022 in our reproductive medicine center， 48 women undergoing in-vitro fertilization （IVF） were enrolled and divided into the antagonist group and the agonist group according to the ovarian stimulation protocol. Follicular fluid samples were collected on the day of oocyte pick-up and granulosa cells were extracted from follicles of different diameters： small （<13 mm）， medium （13~18 mm） and large （≥18 mm）. After RNA quantification， 22 cases （66 samples） were included for analysis and mRNA expression levels of AQPs were compared among the three follicle groups. ResultsThe mRNA expression of aquaporin 2 （AQP2） in luteinized granulosa cells increased with the increase of follicle diameter （linear trend P = 0.004） and the difference was statistically significant between two groups of large and small follicles （P = 0.017）. Statistical difference was found in the antagonist group （P = 0.049 6）， but not in the agonist group （P = 0.108）. ConclusionThe mRNA level of AQP2 in luteinized granulosa cells increases with the increase of follicle diameter and its expression is related to the ovarian stimulation protocol， suggesting that AQP2 may play a role in follicle growth and follicular fluid formation， and its mRNA expression level may be regulated by follicle stimulating hormone （FSH） and luteinizing hormone （LH）.

Luteolin ameliorates loperamide-induced functional constipation in mice

Functional constipation (FC) is one of the most common gastrointestinal disorders characterized by hard stools and infrequent bowel movements, which is associated with dysfunction of the enteric nervous system and intestinal motility. Luteolin, a naturally occurring flavone, was reported to possess potential pharmacological activities on intestinal inflammation and nerve injury. This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh), as well as interstitial cells of Cajal (ICC) biomarker KIT proto-oncogene, receptor tyrosine kinase (C-Kit), and anoctamin-1 (ANO1), implying that luteolin mediated enhancement of colonic function and contributed to the anti-intestinal dysmotility against loperamide-induced FC. Additionally, luteolin decreased the upregulation of aquaporin (AQP)-3, AQP-4, and AQP-8 in the colon of FC mice. In summary, our data showed that luteolin might be an attractive option for developing FC-relieving medications.

Different expressions of aquaporin water channels and macrophages infiltration in human cervix remodeling during pregnancy.

Despite aquaporin water channels (AQPs) play a critical role in maintaining water homeostasis in female reproductive tract and prompt a gradual increase in water content in cervical edema as pregnancy progressed, their relationship with macrophage infiltration and collagen content in human cervical remodeling need to be further investigated. This is the first study to examine the expression and localization of AQP3, AQP4, AQP5, AQP8, and macrophages simultaneously in human cervical ripening. The immunoreactivity of these AQPs was 2.6 to 6-fold higher on gestational weeks 26 (GD26W) than that on GD6W and GD15W, but AQP4 expression on GD39W dropped a similar extent on GD15W, other AQPs continued to rise on GD39W. The AQP3, AQP4, and AQP5 intensity seemed more abundant in cervical stroma than in the perivascular area on GD26W; the distribution of AQP3, AQP5, and AQP8 in cervical stroma was equivalent to that in the perivascular area on GD39W. Macrophage numbers were 1.7-fold higher in subepithelium region and 3.0-fold higher in center area on GD26W than that on GD15W; such numbers remained elevated on GD39W. The electron micrographs showed that cervical extensibility increased significantly on GD26W and GD39W accompanied with increased macrophage infiltration, cervical water content, and much more space among collagen fibers. These findings suggest that the upregulation of AQPs expression in human cervix is closely related to enhanced macrophage infiltration during pregnancy; there may be a positive feedback mechanism between them to lead the increase of water content and the degradation of collagen.