Perturbation of the circadian clock contributes to radiotherapy-induced salivary gland hypofunction
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ABSTRACT:
PROVIDER: PRJNA983230 | ENA |
REPOSITORIES: ENA
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Project description:Salivary gland hypofunction is a common adverse effect during and after radiotherapy of head and neck cancers, resulting in the dry mouth syndrome called xerostomia. Previous studies suggested that the functionality of the salivary gland is under the regulation of the circadian clock, however, the extent and scope of this regulation remains unexplored. Here, we profiled the diurnal fluctuation of gene expression in the mouse submandibular salivary gland. We further analyzed the regulatory role of key circadian transcription factors Bmal1, Nr1d1 (Rev-erba), and Dbp, which revealed a wide range of potential down-stream target genes. The circadian clock was disrupted upon irradiation, as revealed by gene expression analysis. We propose that the mechanism of salivary gland hypofunction in radiotherapy involves perturbation of the circadian clock.
2024-01-01 | GSE234789 | GEO
Project description:Ionizing radiation (IR) – induced salivary gland damage is a common adverse effect in radiotherapy for patients with head and neck cancers. Currently, there is no effective treatment for the resulting salivary gland hypofunction and xerostomia (dry mouth). Here we profiled the acute gene expression change in the mouse submandibular salivary gland, and defined its damage response patterns at the transcriptome level.
2021-09-23 | GSE184673 | GEO
Project description:Objectives: Salivary glands are affected during radiotherapy in the head and neck region, leading to a reduction in salivary flow and changes its composition. Besides negatively affecting the oral soft tissues, this can also lead to dental impairment. Thus, we evaluated the effect of radiotherapy in the proteomic profile of the saliva in patients with head-and-neck-cancer (HNC). Materials and methods: HNC patients had their saliva collected before (BRT), during (2-5 weeks; DRT) and after (3-4 months; ART) radiotherapy. Saliva was also collected from healthy volunteers (control; C). Samples were processed for proteomic analysis. Results: In total 1.055 proteins were identified, among which 46 were common to all groups, while 86, 86, 286 and 395 were exclusively found in C, BRT, DRT and ART, respectively. Remarkably, alpha-enolase was increased 35-fold DRT compared with BRT, while proline-rich proteins were decreased. ART there was a 16-fold increase in scaffold attachment factor-B1 and a 3-fold decrease in alpha-enolase and several cystatins. When compared with C, salivary proteins of BRT patients showed increases cystatin-C, lysozyme C, histatin-1 and proline-rich proteins. Conclusion/Clinical revelance: Both HNC and radiotherapy remarkably change the salivary protein composition. Altogether, our results, for the first time, suggest investigating alpha-enolase levels in saliva DRT in future studies as a possible biomarker and strategy to predict the efficiency of the treatment. Moreover, our data provide important insights for designing dental products that are more effective for these patients and contribute to a better understanding of the progressive changes in salivary proteins induced by radiotherapy.
2021-10-12 | PXD028594 | Pride
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80 degrees C until use. Keywords: SuperSeries This reference Series links data in the following related Series: GSE3746 Circadian skeletal muscle_wt and Clock mutants GSE3748 Circadian liver_wt and Clock mutants
2010-06-12 | E-GEOD-3751 | biostudies-arrayexpress
Project description:The circadian clock is comprised of proteins that form negative feedback loops, which regulate the timing of global gene expression in a coordinated 24 hour cycle. As a result, the plant circadian clock is responsible for regulating numerous physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have combined high-throughput RNA-sequencing and mass spectrometry to comparatively characterize the lhycca1, prr7prr9, gi and toc1 circadian clock mutant rosette transcriptome and proteome at the end-of-day and end-of-night.
2018-01-02 | PXD004763 | Pride
Project description:Radiotherapy of head and neck cancer is accompanied by unavoidable co-irradiation of the salivary gland, often resulting in hyposalivation and reduced quality of life. Irradiated salivary gland tissue is characterized by the presence of cellular senescence, fibrosis, and a chronic inflammatory state changing the cellular microenvironment. These microenvironmental changes may be unfavorable for the regenerative potential of tissue stem cells inhibiting regenerative medicine options. Therefore, we investigated microenvironmental changes of the irradiated murine salivary gland and their effect on the potency of salivary gland stem/progenitor cells (SGSCs). After 15 Gy local irradiation of murine salivary glands, alongside an in time advancing decline in function, the submandibular gland (SMG) showed extensive fibrosis, p21-expressing senescent cells, and immune cell infiltration, all indicative of microenvironmental changes. Additionally, irradiated SMG contained a lower number of CD24++/CD29++ and CD24++/CD29+ stem/progenitor cell enrichment marker-expressing cells 30 days post-irradiation which coincides with a reduction in salisphere formation potential over time. However, after subsequent passaging of organoids derived from glands obtained 14 days after irradiation, and to a lesser extent at 30 days post-irradiation, the ability to form secondary organoids recovered to control levels. In contrast, cells obtained from glands at 90, 180, and 360 days post-irradiation irreversibly lost their ability to form organoids, indicating a time-dependent loss of regenerative potential. Transcriptomic analysis showed overexpression of Bmp4 in day 90 organoids derived from irradiated glands compared to the ones from day 14. Inhibition of Bmp4 using Noggin reversed this adverse response suggesting an important role in modulating SGSC function. Thus, early after irradiation, the regenerative potential of surviving SGSCs is preserved and comparable to that of unirradiated cells. At later time points after irradiation, SGSCs lose their regenerative potential suggesting that the prolonged exposure to a deleterious microenvironment leads to an irreversible decline in stemness. Modulation of Bmp4 signaling pathway might improve the regenerative potential of surviving SGSCs and enhance the efficiency of stem cell therapy in restoring the functionality of irradiated salivary glands.
2022-07-21 | GSE208387 | GEO
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ?l RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80?C until use. Keywords: time course duplicates consisted of pools from independent mice
2010-06-11 | E-GEOD-3748 | biostudies-arrayexpress
Project description:Salivary glands that produce and secret saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we established long-term murine salivary gland organoids from 3 major salivary glands, including parotid gland (PG), submandibular gland (SMG), and sublingual gland (SLG). Murine salivary gland organoids expressed gland-specific genes and proteins of acinar, myoepithelial, and duct cells. Organoids were maintained in growth media (named GEM) and further underwent differentiation in differentiation media (named DAM). Our study will provide an experimental platform for the exploration of mechanisms involvled in tissue regeneration, development, or several salivary gland diseases.
2022-05-05 | GSE184091 | GEO
Project description:Influence of diet and neuronal clk (clock) activity on hemolymph proteomics. We have shown that as photoreceptors die (in the fly) they necrose, which results in their intercellular contents leaking into the hemolymph. We hypothesize that this process is regulated by diet and circadian clock control.
Analysis of differential protein expression in the hemolymph from flies reared on a high protein diet. Comparison of flies with and without a functional circadian clock within their photoreceptors.
Species/Strain: Drosophila, Elav-GeneSwitch-GAL4>UAS-Clk-DN1 (+/- RU486), female
2021-01-30 | MSV000086781 | MassIVE
Project description:Loss of Irf6 leads to disruption of branching morphogenesis and secretory acnii formation in salivary gland. To determine the differentially expressed genes in Irf6 mutant, embryonic salivary gland tissues were extracted at E14.5.
2017-07-29 | GSE102020 | GEO