Dexamethasone-mediated oncogenicity in vitro and in an animal model of glioblastoma

OBJECTIVEDexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug’s impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug’s impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort.METHODSExpression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520).RESULTSThe mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature.CONCLUSIONSThe authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients’ prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.

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Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow

Blood ◽

10.1182/blood-2010-04-278192 ◽

2010 ◽

Vol 116 (15) ◽

pp. e66-e73 ◽

Cited By ~ 104

Author(s):

Chih-Wen Ni ◽

Haiwei Qiu ◽

Amir Rezvan ◽

Kihwan Kwon ◽

Douglas Nam ◽

...

Keyword(s):

Carotid Artery ◽

Ex Vivo ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Gene Expression Profiles ◽

Disturbed Flow ◽

A Genome ◽

Pattern Comparison

Abstract Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.

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Gene expression in mouse ovarian follicle development in vivo versus an ex vivo alginate culture system

Reproduction ◽

10.1530/rep-10-0481 ◽

2011 ◽

Vol 142 (2) ◽

pp. 309-318 ◽

Cited By ~ 26

Author(s):

Elizabeth M Parrish ◽

Anaar Siletz ◽

Min Xu ◽

Teresa K Woodruff ◽

Lonnie D Shea

Keyword(s):

Gene Expression ◽

Transforming Growth Factor ◽

Ex Vivo ◽

Expression Profiles ◽

Ovarian Follicle ◽

Gene Expression Profiles ◽

Follicle Development ◽

Α Subunit

Ovarian follicle maturation results from a complex interplay of endocrine, paracrine, and direct cell–cell interactions. This study compared the dynamic expression of key developmental genes during folliculogenesis in vivo and during in vitro culture in a 3D alginate hydrogel system. Candidate gene expression profiles were measured within mouse two-layered secondary follicles, multi-layered secondary follicles, and cumulus–oocyte complexes (COCs). The expression of 20 genes involved in endocrine communication, growth signaling, and oocyte development was investigated by real-time PCR. Gene product levels were compared between i) follicles of similar stage and ii) COCs derived either in vivo or by in vitro culture. For follicles cultured for 4 days, the expression pattern and the expression level of 12 genes were the same in vivo and in vitro. Some endocrine (cytochrome P450, family 19, subfamily A, polypeptide 1 (Cyp19a1) and inhibin βA subunit (Inhba)) and growth-related genes (bone morphogenetic protein 15 (Bmp15), kit ligand (Kitl), and transforming growth factor β receptor 2 (Tgfbr2)) were downregulated relative to in vivo follicles. For COCs obtained from cultured follicles, endocrine-related genes (inhibin α-subunit (Inha) and Inhba) had increased expression relative to in vivo counterparts, whereas growth-related genes (Bmp15, growth differentiation factor 9, and kit oncogene (Kit)) and zona pellucida genes were decreased. However, most of the oocyte-specific genes (e.g. factor in the germline α (Figla), jagged 1 (Jag1), and Nlrp5 (Mater)) were expressed in vitro at the same level and with the same pattern as in vivo-derived follicles. These studies establish the similarities and differences between in vivo and in vitro cultured follicles, guiding the creation of environments that maximize follicle development and oocyte quality.

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Inhibition of DKC1 induces telomere-related senescence and apoptosis in lung adenocarcinoma

Journal of Translational Medicine ◽

10.1186/s12967-021-02827-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Guangyan Kan ◽

Ziyang Wang ◽

Chunjie Sheng ◽

Chen Yao ◽

Yizhi Mao ◽

...

Keyword(s):

Gene Expression ◽

Lung Adenocarcinoma ◽

Cell Lines ◽

Ectopic Expression ◽

Clinical Information ◽

Cell Senescence ◽

The Cancer Genome Atlas ◽

Poor Overall Survival

Abstract Background Lung cancer is one of the most widely spread cancers in the world and half of the non-small cell lung cancers are lung adenocarcinoma (LUAD). Although there were several drugs been approved for LUAD therapy, a large portion of LUAD still cannot be effectively treated due to lack of available therapeutic targets. Here, we investigated the oncogenic roles of DKC1 in LUAD and its potential mechanism and explored the possibility of targeting DKC1 for LUAD therapy. Methods The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas Program (TCGA) databases were used to examine the DKC1 transcript levels. Gene expression with clinical information from tissue microarray of LUAD were analyzed for associations between DKC1 expression and LUAD prognosis. In addition, loss- and gain-of-function assays were used for oncogenic function of DKC1 both in vitro and in vivo. Results DKC1 is overexpressed in LUAD compared with adjacent normal tissues. High expression of DKC1 predicts the poor overall survival. DKC1 knockdown in LUAD cell lines induced G1 phase arrest and inhibited cell proliferation. Ectopic expression of DKC1 could rescue the growth of LUAD cell lines. In addition, the abundance of DKC1 is positively correlated with telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) levels in LUAD. DKC1 downregulation resulted in decreased TERC expression, reduced telomerase activity and shorten telomere, and thus eventually led to cell senescence and apoptosis. Conclusions Our results show that high DKC1 expression indicates poor prognosis of LUAD and DKC1 downregulation could induce telomere-related cell senescence and apoptosis. This study suggests that DKC1 could serve as a candidate diagnostic biomarker and therapeutic target for LUAD.

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P13.10 Chemoattraction of glioma cells in a local hydrogel trap and immune control associated with improved survival and cognitive functions in a mouse model of glioblastoma resection

Neuro-Oncology ◽

10.1093/neuonc/noab180.118 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii34-ii34

Author(s):

H Castel ◽

E Laillet De Montulle ◽

M Dubois ◽

F Ferracci ◽

A Mutel ◽

...

Keyword(s):

Mouse Model ◽

Cognitive Functions ◽

Ex Vivo ◽

Glioma Cells ◽

Boyden Chamber ◽

Synthetic Analog ◽

Normal Brain ◽

Urotensin Ii

Abstract BACKGROUND Glioblastoma (GB) is the most aggressive brain primary tumor. The prognosis remains poor mainly due to the invasiveness of glioma cells, radio and/or chemoresistance and GB-induced immunosuppressive environment. Here, we propose to use a local delivery system based on a biocompatible hydrogel containing the chemopeptide urotensin II (hUII) or a biased synthetic analog DAB8-hUII, to “trap” GB cells, and/or to control immune cells expressing its G protein-coupled receptor UT, leading to tumor regression and neurological benefit, in a mouse model of GB resection. MATERIAL AND METHODS In vitro, invasion towards UII/analog across different hydrogels or glue of human or murine GB-GFP cell lines was evaluated in Boyden chamber and cloning ring assays. In vivo GB cells were intrastriatally xenografted, then resected while hydrogel- or glue-containing UII/analog was injected in the cavity resection. Behavioral tests, brain immunohistochemical analyses and mouse survival were then investigated. RESULTS In vitro, invasive capacity of human U87 and 42MG or murine GL261 and CT2A GB cells was stimulated by UII loaded into hydrogel-based hyaluronic acid supplemented with collagen or other chemicals, PNIPAAm-PEG, or thrombin-fibrin glue. In vivo, injection of UII- or DAB8-hUII-loaded glue into the cavity resection of GL261 and CT2A GB in C57BL/6 mice significantly improved survival compared with tumor and resected experimental conditions. Neurological status was also tested before and after GB resection. We found that GL261 and CT2A cell-bearing mice expressed altered spontaneous activity, emotion and cognitive functions. Intracavity injection of the glue improved resignation and anxiety and increased motor activity and cognition with a best cognitive recovery with hUII and DAB-8-hUII-loaded glue groups. Ex vivo brain analyses revealed high expression of UT and UII in some GB GFP-positive cells and macrophages within GB core and at the interface with the normal brain, GB cells expressing UT migrating along tortuous podocalyxin+ vascular components. In brains bearing hydrogel/hUII glue, vascularization appears modified and GFAP+ astrocytes and F4/80+ macrophages were highly recruited in the border of the cavity, compared with the other conditions. CONCLUSION A local glue containing UII may trap GB cells and remodel the tumor microenvironment responsible for survival and cognitive improvements, providing new option in the therapeutic arsenal of GB.

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Intestinal Epithelial CD98 Directly Modulates the Innate Host Response to Enteric Bacterial Pathogens

Infection and Immunity ◽

10.1128/iai.01388-12 ◽

2013 ◽

Vol 81 (3) ◽

pp. 923-934 ◽

Cited By ~ 19

Author(s):

Moiz A. Charania ◽

Hamed Laroui ◽

Hongchun Liu ◽

Emilie Viennois ◽

Saravanan Ayyadurai ◽

...

Keyword(s):

Intestinal Inflammation ◽

Ex Vivo ◽

Host Cells ◽

Intestinal Epithelial ◽

Extracellular Loop ◽

Ki 67 ◽

Content Type ◽

Direct Binding

ABSTRACTCD98 is a type II transmembrane glycoprotein whose expression increases in intestinal epithelial cells (IECs) during intestinal inflammation. EnteropathogenicEscherichia coli(EPEC) is a food-borne human pathogen that attaches to IECs and injects effector proteins directly into the host cells, thus provoking an inflammatory response. In the present study, we investigated CD98 and EPEC interactionsin vitroandex vivoand examined FVB wild-type (WT) and villin-CD98 transgenic mice overexpressing human CD98 in IECs (hCD98 Tg mice) and infected withCitrobacter rodentiumas anin vivomodel.In vivostudies indicated that CD98 overexpression, localized to the apical domain of colonic cells, increased the attachment ofC. rodentiumin mouse colons and resulted in increased expression of proinflammatory markers and decreased expression of anti-inflammatory markers. The proliferative markers Ki-67 and cyclin D1 were significantly increased in the colonic tissue ofC. rodentium-infected hCD98 Tg mice compared to that of WT mice.Ex vivostudies correlate with thein vivodata. Small interfering RNA (siRNA) studies with Caco2-BBE cells showed a decrease in adherence of EPEC to Caco2 cells in which CD98 expression was knocked down.In vitrosurface plasmon resonance (SPR) experiments showed direct binding between recombinant hCD98 and EPEC/C. rodentiumproteins. We also demonstrated that the partial extracellular loop of hCD98 was sufficient for direct binding to EPEC/C. rodentium. These findings demonstrate the importance of the extracellular loop of CD98 in the innate host defense response to intestinal infection by attaching and effacing (A/E) pathogens.

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Enhanced SMARCD1, a subunit of the SWI/SNF complex, promotes liver cancer growth through the mTOR pathway

Clinical Science ◽

10.1042/cs20200244 ◽

2020 ◽

Vol 134 (12) ◽

pp. 1457-1472

Author(s):

Yongjie Zhou ◽

Qing Xu ◽

Lv Tao ◽

Yuwei Chen ◽

Yuke Shu ◽

...

Keyword(s):

Liver Cancer ◽

Target Genes ◽

Critical Role ◽

Clinical Information ◽

Normal Liver ◽

The Cancer Genome Atlas ◽

Cancer Growth ◽

Interaction Domain

Abstract The chromatin remodeling complex SWI/SNF regulates the accessibility of target genes to transcription factors and plays a critical role in the tumorigenesis of hepatocellular carcinoma (HCC). The SWI/SNF complex is assembled from approximately 15 subunits, and most of these subunits have distinct roles and are often aberrantly expressed in HCC. A comprehensive exploration of the expression and clinical significance of these subunits would be of great value. In the present study, we obtained the gene expression profile of each SWI/SNF subunit and the corresponding clinical information from The Cancer Genome Atlas (TCGA). We found that 14 out of the 15 SWI/SNF subunits were significantly increased in HCC tissues compared with paired normal liver tissues, and 11 subunits were significantly associated with overall survival (OS). We identified a four-gene prognostic signature including actin-like 6A (ACTL6A), AT-rich interaction domain 1A (ARID1A), SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily C member 1 (SMARCC1) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily D, member 1 (SMARCD1) that could effectively predict OS in HCC patients. Among the genes, SMARCD1 has the most prognostic value. We further conducted in vitro and in vivo experiments and revealed that SMARCD1 promotes liver cancer growth by activating the mTOR signaling pathway. In conclusion, our study has revealed that the expression of SWI/SNF complex subunits, especially SMARCD1, is highly associated with HCC development and acts as a promising prognostic predictor.

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ZDHHC22-Mediated mTOR Palmitoylation Determines Breast Tumor Growth and Endocrine Therapy Sensitivity

10.21203/rs.3.rs-171315/v1 ◽

2021 ◽

Author(s):

Jiefeng Huang ◽

Jie Li ◽

Jun Tang ◽

Yushen Wu ◽

Ziying Yi ◽

...

Keyword(s):

Breast Cancer ◽

Expression Profiles ◽

Methylation Status ◽

The Cancer Genome Atlas ◽

Site Mutation ◽

Western Blots ◽

Tamoxifen Resistant ◽

First Time

Abstract BackgroundPalmitoylation is essential for classic hallmarks of cancer, regulating protein stability and protein-protein interactions. Targeting palmitoylation or palmitoyltransferases has become a novel strategy for therapeutic intervention in cancer. However, few studies have reported the expression pattern, pathological functions and underlying mechanism of ZDHHC22 in breast cancer.MethodsPublic database analysis, quantitative reverse transcription PCR, and western blot were used to analyze ZDHHC22 expression. Methylation-specific PCR was employed to detect the promoter methylation status. Expression of mTOR was examined by immunofluorescence staining and western blots, and palmitoylation of mTOR was detected by acyl-biotin exchange assays. Cellular functions were evaluated via corresponding molecular biological and cellular approaches. Nude mice were used to generate a xenograft tumor model.ResultsWe investigated the expression profiles of 23 palmitoyltransferases using data from The Cancer Genome Atlas and found that ZDHHC22 is frequently expressed at minimal levels in multiple cancers. Downregulation of ZDHHC22 is associated with methylation of its promoter in breast cancer. Ectopic ZDHHC22 expression inhibits the malignant properties of breast cancer both in vitro and in vivo. The enzyme-active site-mutation ZDHHC22-(C111A) mutation reversed these effects, demonstrating that ZDHHC22 suppresses the malignant properties of breast cancer through palmitoylation. Bioinformatics analysis predicted mTOR as the substrate of ZDHHC22. mTOR palmitoylation for the first time was detected and we found ZDHHC22 reduced the stability of mTOR via regulating the palmitoylation of mTOR. Additionally, mTOR expression was frequently negatively correlated with ZDHHC22 in tamoxifen-resistant breast cancer cells and ectopic ZDHHC22 could restore endocrine sensitivity in tamoxifen-resistant breast cancer cell line.ConclusionOur results demonstrating the hypermethylated status and potential tumor suppressor function of ZDHHC22 in breast cancer for the first time established a regulatory mechanism between ZDHHC22 and mTOR palmitoylation, which may pave the way for the development of promising therapeutics that restore endocrine sensitivity.

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Development of a Prognostic Five-Gene Signature for Diffuse Lower-Grade Glioma Patients

Frontiers in Neurology ◽

10.3389/fneur.2021.633390 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiang Zhang ◽

Wenhao Liu ◽

Shun-Bin Luo ◽

Fu-Chen Xie ◽

Xiao-Jun Liu ◽

...

Keyword(s):

Expression Profiles ◽

Clinical Information ◽

Predictive Performance ◽

Risk Groups ◽

Gene Signature ◽

High Risk Group ◽

The Cancer Genome Atlas ◽

Lower Grade ◽

Good Prospect ◽

Genome Atlas

Background: Diffuse lower-grade gliomas (LGGs) are infiltrative and heterogeneous neoplasms. Gene signature including multiple protein-coding genes (PCGs) is widely used as a tumor marker. This study aimed to construct a multi-PCG signature to predict survival for LGG patients.Methods: LGG data including PCG expression profiles and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Survival analysis, receiver operating characteristic (ROC) analysis, and random survival forest algorithm (RSFVH) were used to identify the prognostic PCG signature.Results: From the training (n = 524) and test (n = 431) datasets, a five-PCG signature which can classify LGG patients into low- or high-risk group with a significantly different overall survival (log rank P < 0.001) was screened out and validated. In terms of prognosis predictive performance, the five-PCG signature is stronger than other clinical variables and IDH mutation status. Moreover, the five-PCG signature could further divide radiotherapy patients into two different risk groups. GO and KEGG analysis found that PCGs in the prognostic five-PCG signature were mainly enriched in cell cycle, apoptosis, DNA replication pathways.Conclusions: The new five-PCG signature is a reliable prognostic marker for LGG patients and has a good prospect in clinical application.

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Enhanced Hsa-miR-181d/p-STAT3 and Hsa-miR-181d/p-STAT5A Ratios Mediate the Anticancer Effect of Garcinol in STAT3/5A-Addicted Glioblastoma

Cancers ◽

10.3390/cancers11121888 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1888 ◽

Cited By ~ 10

Author(s):

Heng-Wei Liu ◽

Peter Mingjui Lee ◽

Oluwaseun Adebayo Bamodu ◽

Yu-Kai Su ◽

Iat-Hang Fong ◽

...

Keyword(s):

Ex Vivo ◽

Xenograft Model ◽

Inverse Correlation ◽

The Cancer Genome Atlas ◽

Anticancer Effect ◽

Garcinia Indica ◽

Mouse Xenograft Model ◽

Recurrent Gbm

Background: Glioblastoma (GBM), a malignant grade IV tumor, is the most malignant brain tumor due to its hyper-proliferative and apoptosis-evading characteristics. The signal transducer and activators of transcription (STAT) family genes, including STAT3 and STAT5A, have been indicated to play important roles in GBM progression. Increasing number of reports suggest that garcinol, a polyisoprenylated benzophenone and major bioactive component of Garcinia indica contains potent anti-cancer activities. Material and Methods: The present study investigated the anti-GBM effects of garcinol, focusing on the STAT3/STAT5A activation, using a combination of bioinformatics, in vitro, and ex vivo assays. Results: Our bioinformatics analysis of The Cancer Genome Atlas (TCGA)–GBM cohort (n = 173) showed that STAT3 and STAT5A are preferentially elevated in primary and recurrent GBM, compared to non-tumor brain tissues, and is significantly correlated with reduced overall survival. In support, our immunohistochemical staining of a GBM cohort (n = 45) showed an estimated 5.3-fold (p < 0.001) elevation in STAT3 and STAT5A protein expression in primary and recurrent GBM versus the non-tumor group. In vitro, garcinol treatment significantly suppressed the proliferative, invasive, and migratory potential of U87MG or GBM8401 cells, dose-dependently. In addition, garcinol anticancer effect significantly attenuated the GBM stem cell-like phenotypes, as reflected by diminished ability of U87MG or GBM8401 to form colonies and tumorspheres and suppressed expression of OCT4 and SOX2. Furthermore, analysis on GBM transcriptome revealed an inverse correlation between the level of STAT3/5A and hsa-miR-181d. Garcinol-mediated anti-GBM effects were associated with an increased hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratio. The results were further verified in vivo using U87MG mouse xenograft model where administration of garcinol significantly inhibited tumor growth. Conclusions: We present evidence of anti-GBM efficacy of garcinol mediated by enhancing the hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratios in GBM cells. Our findings suggest a potential new therapeutic agent for combating aggressive GBM.

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Strong correlation between air-liquid interface cultures and in vivo transcriptomics of nasal brush biopsy

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00050.2020 ◽

2020 ◽

Vol 318 (5) ◽

pp. L1056-L1062 ◽

Cited By ~ 1

Author(s):

Baishakhi Ghosh ◽

Bongsoo Park ◽

Debarshi Bhowmik ◽

Kristine Nishida ◽

Molly Lauver ◽

...

Keyword(s):

Epithelial Cells ◽

Strong Correlation ◽

Ex Vivo ◽

Expression Profiles ◽

Liquid Interface ◽

Brush Biopsy ◽

Chronic Respiratory Diseases ◽

Air Liquid Interface

Air-liquid interface (ALI) cultures are ex vivo models that are used extensively to study the epithelium of patients with chronic respiratory diseases. However, the in vitro conditions impose a milieu different from that encountered in the patient in vivo, and the degree to which this alters gene expression remains unclear. In this study we employed RNA sequencing to compare the transcriptome of fresh brushings of nasal epithelial cells with that of ALI-cultured epithelial cells from the same patients. We observed a strong correlation between cells cultured at the ALI and cells obtained from the brushed nasal epithelia: 96% of expressed genes showed similar expression profiles, although there was greater similarity between the brushed samples. We observed that while the ALI model provides an excellent representation of the in vivo airway epithelial transcriptome for mechanistic studies, several pathways are affected by the change in milieu.

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