Aquaporin Inhibitors

Wang, Shuyuan; Solenov, Evgeniy I.; Yang, Baoxue

doi:10.1007/978-981-19-7415-1_22

Cited by 9 publications

(6 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The observed decrease in its expression in IBD patients aligns with previous research findings ( 50 , 51 ). However, it’s important to note that discovering inhibitors for AQP proteins poses a significant challenge due to their perceived ‘undruggable’ properties ( 52 ). Among other down regulated genes, CLDN8 (Claudin 8) a tight junction protein involved in maintaining the integrity of the intestinal barrier known to be down-regulated in both UC and CD ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach

Stemmer,

Zahavi,

Kellerman

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundUnderstanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic targets and novel biomarkers that can aid in the diagnosis of the disease.MethodsTo obtain the largest possible number of samples and analyze them comprehensively, we used a mega-analysis approach. This involved reprocessing raw data from multiple studies and analyzing them using bioinformatic and machine learning techniques.ResultsWe analyzed a total of 697 intestinal biopsies of Ulcerative Colitis (n = 386), Crohn’s disease (n = 183) and non-IBD controls (n = 128). A machine learning analysis detected 34 genes whose collective expression effectively distinguishes inflamed biopsies of IBD patients from non-IBD control samples. Most of these genes were upregulated in IBD. Notably, among these genes, three novel lncRNAs have emerged as potential contributors to IBD development: ENSG00000285744, ENSG00000287626, and MIR4435-2HG. Furthermore, by examining the expression of 29 genes, among the 34, in blood samples from IBD patients, we detected a significant upregulation of 12 genes (p-value < 0.01), underscoring their potential utility as non-invasive diagnostic biomarkers. Finally, by utilizing the CMap library, we discovered potential compounds that should be explored in future studies for their therapeutic efficacy in IBD treatment.ConclusionOur findings contribute to the understanding of IBD pathogenesis, suggest novel biomarkers for IBD diagnosis and offer new prospects for therapeutic intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach

Stemmer,

Zahavi,

Kellerman

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…In addition, another sulfonamide acetazolamide can reduce the level of AQP1 protein by inhibiting the activation of the NF-κB pathway or the Wnt/β-catenin pathway. However, it seems not clear yet whether acetazolamide directly binds to AQP1 and inhibits its function by blocking the pore or only reduces AQP1 mRNA expression [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy?

Rump,

Koos,

Ziehe

et al. 2024

IJMS

View full text Add to dashboard Cite

Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 (Aqp5) knockdown provided enhanced sepsis survival in a murine sepsis model. Potential AQP5 inhibitors provide sulfonamides and their derivatives. In this study, we tested the hypothesis that sulfonamides reduce AQP5 expression in different conditions. The impact of sulfonamides on AQP5 expression and immune cell migration was examined in cell lines REH and RAW 264.7 by qPCR, Western blot and migration assay. Subsequently, whether furosemide and methazolamide are capable of reducing AQP5 expression after LPS incubation was investigated in whole blood samples of healthy volunteers. Incubation with methazolamide (10−5 M) and furosemide (10−6 M) reduced AQP5 mRNA and protein expression by about 30% in REH cells. Pre-incubation of the cells with methazolamide reduced cell migration towards SDF1-α compared to non-preincubated cells to control level. Pre-incubation with methazolamide in PBMCs led to a reduction in LPS-induced AQP5 expression compared to control levels, while furosemide failed to reduce it. Methazolamide appears to reduce AQP5 expression and migration of immune cells. However, after LPS administration, the reduction in AQP5 expression by methazolamide is no longer possible. Hence, our study indicates that methazolamide is capable of reducing AQP5 expression and has the potential to be used in sepsis prophylaxis.

show abstract

“…Another study found that TGN-020 could reduce the expression of AQP4 mRNA and protein in A549 cells exposed to silicon dioxide [ 36 ]. Therefore, some scholars suggested defining TGN-020 as an AQP4 modulator rather than an AQP4 inhibitor [ 37 ]. The dual effects on AQP4 indicate that TGN-020 is a promising agent for the treatment of hydrocephalus after IVH.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 4 Mediates the Effect of Iron Overload on Hydrocephalus After Intraventricular Hemorrhage

et al. 2023

View full text Add to dashboard Cite

Background Iron overload plays an important role in hydrocephalus development following intraventricular hemorrhage (IVH). Aquaporin 4 (AQP4) participates in the balance of cerebrospinal fluid secretion and absorption. The current study investigated the role of AQP4 in the formation of hydrocephalus caused by iron overload after IVH. Methods There were three parts to this study. First, Sprague–Dawley rats received an intraventricular injection of 100 µl autologous blood or saline control. Second, rats had IVH and were treated with deferoxamine (DFX), an iron chelator, or vehicle. Third, rats had IVH and were treated with 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a specific AQP4 inhibitor, or vehicle. Rats underwent T2-weighted and T2* gradient-echo magnetic resonance imaging to assess lateral ventricular volume and intraventricular iron deposition at 7, 14, and 28 days after intraventricular injection and were then euthanized. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence analyses were conducted on the rat brains to evaluate the expression of AQP4 at different time points. Hematoxylin and eosin–stained brain sections were obtained to assess the ventricular wall damage on day 28. Results Intraventricular injection of autologous blood caused a significant ventricular dilatation, iron deposition, and ventricular wall damage. There was increased AQP4 mRNA and protein expression in the periventricular tissue in IVH rats through day 7 to day 28. The DFX treatment group had a lower lateral ventricular volume and less intraventricular iron deposition and ventricular wall damage than the vehicle-treated group after IVH. The expression of AQP4 protein in periventricular tissue was also inhibited by DFX on days 14 and 28 after IVH. The use of TGN-020 attenuated hydrocephalus development after IVH and inhibited the expression of AQP4 protein in the periventricular tissue between day 14 and day 28 without a significant effect on intraventricular iron deposition or ventricular wall damage. Conclusions AQP4 located in the periventricular area mediated the effect of iron overload on hydrocephalus after IVH.

show abstract

Aquaporin Inhibitors

Cited by 9 publications

References 58 publications

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach

Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy?

Aquaporin 4 Mediates the Effect of Iron Overload on Hydrocephalus After Intraventricular Hemorrhage

Contact Info

Product

Resources

About