1.METTL3-mediated m6A RNA methylation regulates dorsal lingual epithelium homeostasis.
Qiuchan XIONG ; Caojie LIU ; Xin ZHENG ; Xinyi ZHOU ; Kexin LEI ; Xiaohan ZHANG ; Qian WANG ; Weimin LIN ; Ruizhan TONG ; Ruoshi XU ; Quan YUAN
International Journal of Oral Science 2022;14(1):26-26
The dorsal lingual epithelium, which is composed of taste buds and keratinocytes differentiated from K14+ basal cells, discriminates taste compounds and maintains the epithelial barrier. N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotic cells. How METTL3-mediated m6A modification regulates K14+ basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear. Here we show knockout of Mettl3 in K14+ cells reduced the taste buds and enhanced keratinocytes. Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds. Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization, but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery. Mechanically, we revealed that the most frequent m6A modifications were enriched in Hippo and Wnt signaling, and specific peaks were observed near the stop codons of Lats1 and FZD7. Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.
Animals
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Epithelium/metabolism*
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Homeostasis
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Methylation
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Methyltransferases/metabolism*
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Mice
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RNA
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Taste Buds/metabolism*
2.The expression of E-cadherin and occludin in epithelium of chronic rhinosinositis and its significance.
Lili SHI ; Xiang LU ; Zheng LIU ; Yonghua CUI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(11):499-506
OBJECTIVE:
To explore the expression and distribution of barrier molecules in epithelium of various types of chronic rhinosinusitis and its significance.
METHOD:
There were four groups including control (13 samples), Eos-CRSwNP (10 samples), nonEos-CRSwNP (14 samples), CRSsNP (11 samples). The method of immunohistochemistry was used to detect the protein expression of E-cadherin and occludin in nasal mucosa.
RESULT:
There was positive staining extensively distributed among cells in nasal mucosa. There was no significant difference in these groups. However, the occludin mainly located on the top of epithelial cells. In normal nasal mucosa, the positive expression was continuous, however, it was discontinuous both in CRSwNP and CRSsNP groups.
CONCLUSION
There was no E-cadherin loss in the progression of pathophysiology of chronic rhinosinusitis. But the loss of occludin may correlate to the dysfunction of epithelial barrier, which was beneficial for the pathogen invasion.
Cadherins
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metabolism
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Chronic Disease
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Epithelial Cells
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Epithelium
;
metabolism
;
Humans
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Immunohistochemistry
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Nasal Mucosa
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Occludin
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metabolism
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Rhinitis
;
metabolism
;
Sinusitis
;
metabolism
3.MiR-663a Inhibits Radiation-Induced Epithelium-to-Mesenchymal Transition by Targeting TGF-β1.
Pei QU ; Zhi Ang SHAO ; Bing WANG ; Jin Peng HE ; Ya Nan ZHANG ; Wen Jun WEI ; Jun Rui HUA ; Heng ZHOU ; Dong LU ; Nan DING ; Ju Fang WANG
Biomedical and Environmental Sciences 2022;35(5):437-447
Objective:
miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT).
Methods:
TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified.
Results:
Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation.
Conclusion
Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.
Down-Regulation
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Epithelial-Mesenchymal Transition
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Epithelium/metabolism*
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MicroRNAs/metabolism*
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Transforming Growth Factor beta1/pharmacology*
4.Comparative Toxicity of Nanomaterials to Air-blood Barrier Permeability Using an In Vitro Model.
Kang Feng ZHAO ; Yu Qing SONG ; Rui Hua ZHANG ; Xiao Yan YANG ; Bo SUN ; Zhi Quan HOU ; Xiao Ping PU ; Hong Xing DAI ; Xue Tao BAI
Biomedical and Environmental Sciences 2019;32(8):602-613
OBJECTIVE:
To comparatively study the toxicity of four metal-containing nanoparticles (MNPs) and their chemical counterparts to the air-blood barrier (ABB) permeability using an in vitro model.
METHODS:
ABB model, which was developed via the co-culturing of A549 and pulmonary capillary endothelium, was exposed to spherical CuO-NPs (divided into CuO-40, CuO-80, and CuO-100 based on particle size), nano-Al2O3 (sheet and short-rod-shaped), nano-ZnO, nano-PbS, CuSO4, Al2(SO4)3, Zn(CH3COO)2, and Pb(NO3)2 for 60 min. Every 10 min following exposure, the cumulative cleared volume (ΔTCL) of Lucifer yellow by the model was calculated. A clearance curve was established using linear regression analysis of ΔTCL versus time. Permeability coefficient (P) was calculated based on the slope of the curve to represent the degree of change in the ABB permeability.
RESULTS:
The results found the increased P values of CuO-40, CuO-80, sheet, and short-rod-shaped nano-Al2O3, Al2(SO4)3, and Pb(NO3)2. Among them, small CuO-40 and CuO-80 were stronger than CuO-100 and CuSO4; no difference was observed between Al2(SO4)3 and sheet and short-rod-shaped nano-Al2O3; and nano-PbS was slightly weaker than Pb(NO3)2. So clearly the MNPs possess diverse toxicity.
CONCLUSION
ABB permeability abnormality means pulmonary toxicity potential. More studies are warranted to understand MNPs toxicity and ultimately control the health hazards.
A549 Cells
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Blood-Air Barrier
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metabolism
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Epithelium
;
metabolism
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Humans
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Metal Nanoparticles
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toxicity
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Particle Size
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Permeability
5.Histochemical Characterization of the Lectin-binding Sites in the Equine Vomeronasal Organ.
Jee Young LEE ; Tae Young KANG ; Yong Duk LEE ; Tae Kyun SHIN
Journal of Veterinary Science 2003;4(1):15-19
The binding specificities of various lectins, such as the Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), and the Bandeiraea simplicifolia BS-1 (Isolectin B4), Triticum vulgaris (WGA), Arachis hypogaea (PNA), and Ulex europaeus (UEA-I) lectins, were studied in the vomeronasal organ of the horse. The microvilli of the vomeronasal sensory epithelium were positive for DBA, SBA, Isolectin B4, WGA, PNA, and UEA-I. The receptor cells showed intense reactivity for DBA and WGA. Lectins were not detected in the supporting cells or basal cells. The Jacobson's glands were positive for WGA and UEA-I, but lectins were absent from the nerve bundles. From these results, we postulate that several lectin-binding carbohydrates on the microvilli and neurosensory cells are associated with chemoreception in the horse. In addition, the differential lectin-binding patterns in the horse suggest that the carbohydrates present in this particular sense organ are species-specific.
Animals
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Binding Sites
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Epithelium/metabolism
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Horses/anatomy&histology/*metabolism
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Immunohistochemistry/veterinary
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Lectins/*metabolism
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Male
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Protein Binding
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Vomeronasal Organ/*metabolism
6.Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.
Ji DONG ; Xinglong WU ; Xin ZHOU ; Yuan GAO ; Changliang WANG ; Wendong WANG ; Weiya HE ; Jingyun LI ; Wenjun DENG ; Jiayu LIAO ; Xiaotian WU ; Yongqu LU ; Antony K CHEN ; Lu WEN ; Wei FU ; Fuchou TANG
Protein & Cell 2023;14(6):433-447
Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans
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Epigenesis, Genetic
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Gastric Mucosa/metabolism*
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Chromatin/metabolism*
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Stem Cells
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Epithelium/metabolism*
;
Fatty Acid-Binding Proteins/metabolism*
7.E-cadherin and Cytokeratin Subtype Profiling in Effusion Cytology.
Joungho HAN ; Mi Kyung KIM ; Seok Jin NAM ; Jung Hyun YANG
Journal of Korean Medical Science 2004;19(6):826-833
Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic anti-gen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20-expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others.
Cadherins/*metabolism
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Carcinoma/diagnosis/*metabolism/*secondary
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Comparative Study
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Diagnosis, Differential
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Epithelium/*metabolism/*pathology
;
Humans
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Hyperplasia/metabolism
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Immunohistochemistry/methods
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Keratin/*metabolism
;
Mesothelioma/diagnosis/*metabolism
;
Tumor Markers, Biological/*metabolism
8.Glandular odontogenic cyst: report of two cases with cytokeratin 18 expression.
Da-Peng LU ; Ping SHU ; Ru-dong XING ; Yukihiro TATEMOTO ; Tokio OSAKI
Chinese Journal of Stomatology 2007;42(12):741-743
OBJECTIVETo report two cases of glandular odontogenic cyst and examine its cytokeratin 18,19 expression.
METHODSTwo cases of glandular odontogenic cyst were reported and studied. The cytokeratin 18, 19 expression in these two cases were also investigated using immuno-histochemical staining as well as in the situ hybridization of the cyst epithelium.
RESULTSHisto-pathological examination revealed that ciliated columnar cells, squamous cells and low-columnar cells were found in the superficial layer of the lining epithelium. Several minor salivary glands, mainly composed of seromucous cells were observed near the satellite cyst. CK18 were expressed in all layers of the lining epithelium of varying intensity. CK18 was negative in lining epithelium of the daughter cyst, but CK19 was positive. CK18-mRNA was expressed in all the layers of the lining epithelium, the salivary glands and daughter cysts.
CONCLUSIONSHistological features and CK18 expression may be indicative of the possibility of salivary glandular and odontogenic differentiation.
Adolescent ; Adult ; Epithelium ; pathology ; Female ; Humans ; Keratin-18 ; metabolism ; Keratin-19 ; metabolism ; Male ; Odontogenic Cysts ; metabolism ; pathology
10.Degradation of phagosomes and diurnal changes of lysosomes in rabbit retinal pigment epithelium.
Korean Journal of Ophthalmology 1996;10(2):82-91
Diurnal changes of lysosomes including ultrastructural changes of phagosomes and acid phosphatase reactions in phagosomes, as well as diurnal biochemical changes in cathepsin D activity, were studied in the retinal pigment epithelium (RPE) of the rabbit. The rabbit was maintained on a natural light-dark cycle over seven days in fall and was sacrificed at various times during the day and night. The number of lysosomes or phagosomes in the RPE was the highest at 1.5 hours after exposure to sunlight (8:00 AM), and thereafter decreased with time. Three types of phagosomes were observed and acid phosphatase reactions were different in each type of phagosome; the fresh phagosomes were negative or positive, lamellar bodies positive, and dense bodies partially positive. The biochemical activity of cathepsin D was the highest at 8:00 AM, and this was consistent with the time of peak in phagocytic activity in the RPE. This report shows that phagocytic activity in the RPE occurred in the early stage after exposure to sunlight, and that fresh phagosomes were sequentially degraded to lamellar or dense bodies. Cathepsin D activity also increased, and this was consistent with the phagocytic activity in the RPE.
Acid Phosphatase/metabolism
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Animals
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Cathepsin D/metabolism
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Cell Count
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Choroid/metabolism/ultrastructure
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Circadian Rhythm/*physiology
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Lysosomes/*metabolism/ultrastructure
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Phagosomes/*metabolism/ultrastructure
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Pigment Epithelium of Eye/*metabolism/ultrastructure
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Rabbits