Expression and Clinical Significance of Elafin in Inflammatory Bowel Disease

Zhang, Wei; Teng, Guigen; Wu, Ting; Tian, Yu; Wang, Huahong

doi:10.1097/mib.0000000000001252

Cited by 19 publications

(25 citation statements)

References 26 publications

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“…A recent study by Zhang et al compared the expression of elafin in the colonic mucosa of patient with IBD versus that in healthy controls by immunohistochemistry staining and qRT-PCR. 24 They showed that the expression of elafin decreased in patients with active IBD, and was negatively correlated with disease activity, suggesting that elafin may play a protective role in IBD. Thus, it is not surprising to find major downregulation of PI3 in the long-duration UC samples in our study.…”

Section: Discussionmentioning

confidence: 99%

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Low

Mokhtar

Wong

et al. 2019

Journal of Crohn's and Colitis

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Background and aims Patients with ulcerative colitis [UC] with long disease duration have a higher risk of developing colitis-associated cancer [CAC] compared with patients with short-duration UC. The aim of this study was to identify transcriptomic differences associated with the duration of UC disease. Methods We conducted transcriptome profiling on 32 colonic biopsies [11 long-duration UC, ≥20 years; and 21 short-duration UC, ≤5 years] using Affymetrix Human Transcriptome Array 2.0. Differentially expressed genes [fold change > 1.5, p < 0.05] and alternative splicing events [splicing index > 1.5, p < 0.05] were determined using the Transcriptome Analysis Console. KOBAS 3.0 and DAVID 6.8 were used for KEGG and GO analysis. Selected genes from microarray analysis were validated using qPCR. Results There were 640 differentially expressed genes between both groups. The top ten upregulated genes were HMGCS2, UGT2A3 isoforms, B4GALNT2 , MEP1B , GUCA2B , ADH1C , OTOP2 , SLC9A3 , and LYPD8 ; the top ten downregulated genes were PI3 , DUOX2 , VNN1 , SLC6A14 , GREM1 , MMP1 , CXCL1 , TNIP3 , TFF1 , and LCN2 . Among the 123 altered KEGG pathways, the most significant were metabolic pathways; fatty acid degradation; valine, leucine, and isoleucine degradation; the peroxisome proliferator–activated receptor signalling pathway; and bile secretion, which were previously linked with CAC. Analysis showed that 3560 genes exhibited differential alternative splicing between long- and short-duration UC. Among them, 374 were differentially expressed, underscoring the intrinsic relationship between altered gene expression and alternative splicing. Conclusions Long-duration UC patients have altered gene expressions, pathways, and alternative splicing events as compared with short-duration UC patients, and these could be further validated to improve our understanding of the pathogenesis of CAC.

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Section: Discussionmentioning

confidence: 99%

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Low

Mokhtar

Wong

et al. 2019

Journal of Crohn's and Colitis

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“…However, the role of OTX1 in ccRCC is still unknown. PI3, also called elafin, encodes an elastase-specific inhibitor that functions as an antimicrobial peptide [27,28]. Caruso et al demonstrated that elafin predicts poor outcome in ovarian and breast cancer patients, and it may play a role in tumor dormancy; moreover, it has been shown that elafin is an important therapeutic target for breast and ovarian carcinoma [29–31].…”

Section: Discussionmentioning

confidence: 99%

Identification of a 5-Gene Signature Predicting Progression and Prognosis of Clear Cell Renal Cell Carcinoma

et al. 2019

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Background Although the mortality rates of clear cell renal cell carcinoma (ccRCC) have decreased in recent years, the clinical outcome remains highly dependent on the individual patient. Therefore, identifying novel biomarkers for ccRCC patients is crucial. Material/Methods In this study, we obtained RNA sequencing data and clinical information from the TCGA database. Subsequently, we performed integrated bioinformatic analysis that includes differently expressed genes analysis, gene ontology and KEGG pathway analysis, protein-protein interaction analysis, and survival analysis. Moreover, univariate and multivariate Cox proportional hazards regression models were constructed. Results As a result, we identified a total of 263 dysregulated genes that may participate in the metastasis of ccRCC, and established a predictive signature relying on the expression of OTX1, MATN4, PI3, ERVV-2, and NFE4, which could serve as significant progressive and prognostic biomarkers for ccRCC. Conclusions We identified differentially expressed genes that may be involved in the metastasis of ccRCC. Moreover, a predictive signature based on the expression of OTX1, MATN4, PI3, ERVV-2, and NFE4 could be an independent prognostic factor for ccRCC.

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“…The peptidase inhibitor 3 (PI3) gene encodes elafin and demonstrates antimicrobial and anti-inflammatory activities 25 . Elafin has been shown to play a protective role in inflammatory bowel disease 26 , asthma 27 , and has been shown to be downregulated in acute stages of acute respiratory distress syndrome 28 . Elafin has also been proposed to be a modulator of innate immunity in the lower genital tract 29 .…”

Section: Discussionmentioning

confidence: 99%

Differences in maternal gene expression in Cesarean section delivery compared with vaginal delivery

Kothiyal

Schulkers

Hazrati

et al. 2020

Sci Rep

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Cesarean section (CS) is recognized as being a shared environmental risk factor associated with chronic immune disease. A study of maternal gene expression changes between different delivery modes can add to our understanding of how CS contributes to disease patterns later in life. We evaluated the association of delivery mode with postpartum gene expression using a cross-sectional study of 324 mothers who delivered full-term (≥ 37 weeks) singletons. Of these, 181 mothers had a vaginal delivery and 143 had a CS delivery (60 with and 83 without labor). Antimicrobial peptides (AMP) were upregulated in vaginal delivery compared to CS with or without labor. Peptidase inhibitor 3 (PI3), a gene in the antimicrobial peptide pathway and known to be involved in antimicrobial and anti-inflammatory activities, showed a twofold increase in vaginal delivery compared to CS with or without labor (adjusted p-value 1.57 × 10–11 and 3.70 × 10–13, respectively). This study evaluates differences in gene expression by delivery mode and provides evidence of antimicrobial peptide upregulation in vaginal delivery compared to CS with or without labor. Further exploration is needed to determine if AMP upregulation provides protection against CS-associated diseases later in life.

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Expression and Clinical Significance of Elafin in Inflammatory Bowel Disease

Abstract: Elafin decreased in active patients with IBD and was negatively correlated with disease activity, suggesting that elafin may play a protective role and could be used as an index to evaluate disease activity in IBD.

Cited by 19 publications

References 26 publications

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Identification of a 5-Gene Signature Predicting Progression and Prognosis of Clear Cell Renal Cell Carcinoma

Differences in maternal gene expression in Cesarean section delivery compared with vaginal delivery

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