Molecular mechanisms of saliva secretion and hyposecretion

European Journal Of Oral Sciences, Год журнала: 2024, Номер 132(2)

Опубликована: Янв. 8, 2024

Abstract The exocrine salivary gland secretes saliva, a fundamental body component to maintain oral homeostasis. Saliva is composed of water, ions, and proteins such as amylase, mucins, immunoglobulins that play essential roles in the digestion food, lubrication, prevention dental caries periodontitis. An increasing number people experience saliva hyposecretion due aging, medications, Sjögren's syndrome, radiation therapy for head neck cancer. However, current treatments are mostly limited temporary symptomatic relief. This review explores molecular mechanisms underlying secretion provide insight into putative therapeutic targets treatment. Proteins implicated pathways, including Ca 2+ ‐signaling proteins, aquaporins, soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors, tight junctions, aberrantly expressed localized patients with hyposecretion, syndrome. Analysis studies on suggests crosstalk between fluid secretory pathways via /protein kinase C cAMP/protein A regulates secretion. Impaired two may contribute hyposecretion. Future research detailed regulatory information define novel generate strategies

Язык: Английский

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Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats

Experimental Biology and Medicine, Год журнала: 2024, Номер 249

Опубликована: Май 2, 2024

Diabetes mellitus is a prevalent disease that often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) structures responsible for maintaining tear homeostasis, not completely known. It has been shown Opioid Growth Factor Receptor (OGFr), its ligand, (OGF), dysregulated in diabetic rats leading to overproduction inhibitory growth peptide OGF. opioid antagonist naltrexone hydrochloride (NTX) blocks OGF-OGFr pathway, complete blockade following systemic or topical treatment with NTX restores rate re-epithelialization wounds, normalizes sensitivity, reverses dry eye animal models. These effects occur rapidly within days initiating treatment. present study was designed understand mechanisms related fast reversal (<5 days) type 1 (T1D) investigating dysregulation LFU. approach involved examination morphology LFU before after Male female adult Sprague-Dawley were rendered hyperglycemic streptozotocin, 6 weeks considered be T1D model. Rats received twice daily one 10 days. During period treatment, production sensitivity recorded. On day 11, animals euthanized orbital tissues conjunctiva, eyelids, glands, removed processed histologic immunohistochemistry. had significantly insensitivity, number size gland acini, expression aquaporin-5 (AQP5) protein goblet cell size. Thus, restored normal values, increased AQP5 expression, area cells normal. no effect acini conjunctival cells. In summary, pathway reversed complications some components homeostasis confirming efficacy as defects diabetes.

Язык: Английский

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Immunomodulatory effects of Yu-Ping-Feng formula on primary Sjögren syndrome: interrogating the T-cell response

Journal of Leukocyte Biology, Год журнала: 2024, Номер unknown

Опубликована: Июль 2, 2024

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, underlying mechanism immunomodulatory remains challenging, given complicate composition herbal medicines. Here, we developed an immunological approach to interrogate T helper cell response. Through data mining hypothesized that Chinese medicine formula, Yu-Ping-Feng (YPF) might be a promising candidate for treating primary Sjögren's syndrome (pSS), common disease manifested by exocrine gland dysfunction. We took advantage mouse model experimental (ESS) previously established YPF formula treatment. therapy ameliorated ESS pathology mice with active disease, showing improved salivary function and decreased serum levels autoantibodies. Phenotypic analysis suggested both effector B cells were significantly suppressed. Using co-culture assay adoptive transfer models, demonstrated directly restrained effector/memory expansion differentiation into Th17 follicular (Tfh) cells, key subsets pathogenesis. Importantly, recruited 20 pSS patients conducted pilot study 8-week formula. treatment effectively fatigue symptoms, functions reduced IgG/IgA levels, while decreased. There was trend reduction on activity, but not statistically significant. Together, our findings novel assess which may favorable

Язык: Английский

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Reticulated Retinoic Acid Synthesis is Implicated in the Pathogenesis of Dry Eye in Aqp5 Deficiency Mice

Investigative Ophthalmology & Visual Science, Год журнала: 2024, Номер 65(8), С. 25 - 25

Опубликована: Июль 17, 2024

Purpose: Abnormalities in aquaporins are implicated the pathological progression of dry eye syndrome. Retinoic acid (RA) regulates cellular proliferation, differentiation, and apoptosis cornea, thereby being associated with disease (DED). The objective this study is to explore underlying mechanisms responsible for RA metabolic abnormalities corneas lacking aquaporin 5 (AQP5). Methods: Dry (DE) models were induced via subcutaneous scopolamine hydrobromide. Aqp5 knockout (Aqp5−/−) mice DE utilized assess corneal epithelial alterations. Tear secretion, goblet cell counts, punctate defects evaluated. impact on RA-related enzymes receptors was investigated using pharmacological or SR (A JunB inhibitor), a transcription factor inhibitor, treatment mouse cells (CECs), human (HCECs). HCECs NaCl-treated underwent quantitative real-time PCR (qRT-PCR), immunofluorescent, Western blot, TUNEL assays. regulation Aldh1a1 explored ChIP-PCR. Results: reduced both CECs NaCl-induced HCECs. Aqp5−/− exhibited phenotype Aldh1a1. apoptosis, promoted improved mice. enrichment promoter identified by significantly increased expression, Ki67, ΔNp63-positive cells, decreased TUNEL-positive Conclusions: Our findings demonstrated downregulation expression aberrant metabolism conditions. Knockout resulted production through activation JunB, subsequently leading manifestation symptoms.

Язык: Английский

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Distinctive small molecules blend: promotes lacrimal gland epithelial cell proliferation in vitro and accelerates lacrimal gland injury repair in vivo

The Ocular Surface, Год журнала: 2024, Номер 34, С. 283 - 295

Опубликована: Авг. 28, 2024

Язык: Английский

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Causal Relationship Between Sjögren’s Syndrome and Gut Microbiota: A Two-Sample Mendelian Randomization Study

Biomedicines, Год журнала: 2024, Номер 12(10), С. 2378 - 2378

Опубликована: Окт. 18, 2024

Background: Gut microbiota have been previously reported to be related a variety of immune diseases. However, the causal connection between Sjögren’s syndrome (SS) and gut has yet clarified. Methods: We employed two-sample Mendelian randomization (MR) analysis evaluate SS, utilizing summary statistics from genome-wide association studies (GWASs) obtained MiBioGen FinnGen consortia. The inverse variance weighted (IVW) approach represents primary method analysis. Sensitivity was used eliminate instrumental variables heterogeneity horizontal pleiotropy. In addition, we performed an using independent GWAS for SS European Bioinformatics Institute (EBI) dataset further verify our results. Results: IVW results demonstrated that phylum Lentisphaerae (OR = 0.79, 95% CI: 0.63–0.99, p 0.037), class Deltaproteobacteria 0.67, 0.47–0.96, 0.030), family Porphyromonadaceae 0.60, 0.38–0.94, 0.026), genus Eubacterium coprostanoligenes group 0.61, 0.4–0.93, 0.021), Blautia 0.62, 0.43–0.90, 0.012), Butyricicoccus 0.42–0.90, Escherichia.Shigella 0.7, 0.49–0.99, 0.045) Subdoligranulum 0.44–0.86, 0.005) exhibited protective effects on SS. Relevant pleiotropy or not detected. Furthermore, repeating with cohort provided by EBI dataset, only remained significantly associated effect 0.41, 0.18–0.91, 0.029). Two-step MR revealed exerts its reducing CXCL6 levels in (OR, 0.87; CI 0.76–0.99, 0.033). Conclusions: Our study identified multiple genera A two-step result calculated mediated datasets available consortia do provide sufficient information comprehensive demographic data subgroup analyses. Additional validation various omics technologies is necessary comprehend development intricate interplay genes environment over period time.

Язык: Английский

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Myeloid-derived growth factor promotes M2 macrophage polarization and attenuates Sjögren’s syndrome via suppression of the CX3CL1/CX3CR1 axis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 21, 2024

Introduction Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that characterized by the infiltration of immune cells into salivary glands. The re-establishment glands (SGs) function in pSS remains clinical challenge. Myeloid-derived growth factor (MYDGF) has anti-inflammatory, immunomodulatory, and tissue-functional restorative abilities. However, its potential to restore SGs during not yet been investigated. Methods Nonobese diabetic (NOD)/LtJ mice (pSS model) were intravenously administered with adeno-associated viruses carrying MYDGF at 11 weeks age. Salivary flow rates determined before after treatment. Mice killed 5 treatment, submandibular collected for analyses histological scores, inflammatory cell infiltration, PCR determination genes, Western blotting functional proteins. Furthermore, mRNA sequencing bioinformatics used predict mechanism underlying therapeutic effect MYDGF. Results Treatment NOD/LtJ alleviated pSS, as indicated increased rate, reduced lymphocyte attenuated glandular inflammation, enhanced AQP5 NKCC1 expression. gene expression levels cytokines chemokines, including Ccl12, Ccl3, Il1r1 , Ccr2 Cx3cr1 Il7 Mmp2 Mmp14 Il1b significantly decreased treatment MYDGF, RNA sequencing. Meanwhile, inhibits macrophages (Mϕ) SGs, induces polarization M2ϕ, suppresses C-X3C motif ligand 1 (CX3CL1)/C-X3C receptor (CX3CR1) axis. Conclusions Our findings showed could revitalize inhibit Mϕ, promote M2ϕ via suppression CX3CL1/CX3CR1 axis, which implications therapy pSS.

Язык: Английский

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Time-Dependent Analysis of Sicca Symptoms and Anti-Ro/SSA and Anti-La/SSB Antibodies in Patients with AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder

The Tohoku Journal of Experimental Medicine, Год журнала: 2023, Номер 260(3), С. 215 - 221

Опубликована: Янв. 1, 2023

Anti-aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and Sjögren syndrome (SS) are likely comorbidities. However, the exact effects of age disease duration on positivity rates serum anti-Ro/SSA anti-La/SSB (anti-SSA/SSB) antibodies presence sicca symptoms in patients with AQP4-IgG remain unknown. In present study, we evaluated data from suspected NMOSD who had neurological episodes tested for AQP4-IgG. Associations between SS-related findings were evaluated. The anti-SSA/SSB [odds ratio (OR), 7.34; 95% confidence interval (CI), 5.71-9.43; p < 0.0001] that (OR, 2.08; CI, 1.67-2.58; 0.0001) both higher (n = 1,651) than those without 2,796). Meanwhile, neither nor elapsed time onset was linked to prevalence or symptoms, factors elevated since frequency among irrespective 1.11; 0.67-1.85; 0.6892). measured titers did not differ significantly according (p 0.2386; Mann-Whitney U test). summary, producing an AQP4-IgG, implying occurrence comorbid SS is temporarily precede synchronize AQP4-IgG-positive NMOSD.

Язык: Английский

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Insights into the Function of Aquaporins in Gastrointestinal Fluid Absorption and Secretion in Health and Disease

Cells, Год журнала: 2023, Номер 12(17), С. 2170 - 2170

Опубликована: Авг. 29, 2023

Aquaporins (AQPs), transmembrane proteins permeable to water, are involved in gastrointestinal secretion. The secretory products of the glands delivered either some organ cavities for exocrine or bloodstream endocrine glands. main being part system salivary glands, gastric duodenal Brunner’s gland, liver, bile ducts, gallbladder, intestinal goblet cells, and pancreas. Due their expression AQPs fulfill important roles secretion various fluids food handling. This review summarizes contribution physiological pathophysiological stages related

Язык: Английский

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Uncovering the molecular mechanism of Mume Fructus in treatment of Sjögren’s syndrome

Medicine, Год журнала: 2024, Номер 103(19), С. e38085 - e38085

Опубликована: Май 10, 2024

Background: Modern medicine has no cure for the xerostomia caused by early onset of Sjögren’s syndrome. Mume Fructus is a common Chinese herbal used to relieve xerostomia. However, molecular mechanisms effects are unknown. In this study, network pharmacology and docking were investigate action on Materials method: The Traditional Medicine Systems Pharmacology Database Analysis Platform database was identify active components targets Fructus, UniProt genes encoding these targets. SS-related also identified from GeneCards OMIM databases. By finding intersection compounds syndrome, predicted in treatment syndrome obtained. Further investigation their carried out constructing “medicine-candidate compound-target-disease” using Cytoscape 3.7.2, Protein-Protein Interaction STRING key Gene Ontology Kyoto Encyclopedia Genes Genomes enrichment analysis R software. Finally, verify affinity candidate Results: Quercetin, beta-sitosterol, kaempferol interact with AKT1, IL-6, IL-1B, JUN, CASP3, MAPK8. These results suggest that exerts its therapeutic peripheral gland injury secondary cardiovascular disease tumorigenesis through anti-inflammatory, anti-oxidant, anti-tumor pathways. Conclusion: With pharmacology, study systematically main components, targets, specific providing both theoretical basis research direction further investigations Fructus.

Язык: Английский

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