RNA-seq Reveals Transcriptomic Differences in Inflamed and Noninflamed Intestinal Mucosa of Crohn's Disease Patients Compared with Normal Mucosa of Healthy Controls

Sung Noh Hong, Je Gun Joung, Joon Seol Bae, Chan Soo Lee, Ja Seol Koo, Soo Jung Park, Jong Pil Im, You Sun Kim, Ji Won Kim, Woong Yang Park, Young Ho Kim

Research output: Contribution to journalArticle

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Abstract

Background: Aberrant gene expression in the gut mucosa might contribute to the initiation and progression of Crohn's disease (CD). RNA sequencing (RNA-seq) provides precise measurements of expression levels of transcripts and their isoforms. The aim of this study was to use RNA-seq to investigate transcriptomic differences and identify significantly differentially expressed transcripts in inflamed and noninflamed intestinal mucosa of CD patients. Methods: RNA-seq was performed on 13 pairs of inflamed and noninflamed intestinal mucosa from 13 CD patients and on sex-matched normal mucosa of 13 healthy controls. Significantly differentially expressed transcripts were validated by immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction, and enzyme-linked immunosorbent assay. Results: RNA-seq revealed genome-wide transcriptomic differences between normal mucosa, noninflamed, and inflamed CD mucosa. Among 950 differentially expressed genes, 19 were up- or downregulated (upregulation: ANGPT2, CHN1, CPXM1, CPZ, CXCL1, FCN3, GJC1, HSD11B1, LZTS1, MEOX1, MMP12, PLA1A, SERPINE1, SGIP1, and TRPC4; downregulation: FAM189A1, PDE6A, SLC38A4, and HMGCS2) with statistical significance (p < 0.01 and q < 0.05). Among them, CXCL1 exhibited the highest fold change between groups. Immunohistochemistry for CXCL1 revealed no expression in normal mucosa, slightly increased expression in noninflamed CD mucosa, and highly increased expression in inflamed CD mucosa. Quantitative reverse transcriptase polymerase chain reaction showed that CXCL1 expression was significantly associated with epithelial damage, increased infiltration of polymorphonuclear leukocytes, and submucosal fibrosis. Serum CXCL1 concentration measured by enzyme-linked immunosorbent assay was better correlated with CD activity index (r = 0.660) than with C-reactive protein (r = 0.204). Conclusions: RNA-seq revealed transcriptomic differences between normal mucosa, noninflamed CD mucosa, and inflamed CD mucosa. Intestinal and serum CXCL1 was substantially increased with CD activity and can be used as a potential biomarker of CD.

Original languageEnglish
Pages (from-to)1098-1108
Number of pages11
JournalInflammatory Bowel Diseases
Volume23
Issue number7
DOIs
Publication statusPublished - 2017 Jul 1

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RNA Sequence Analysis
Intestinal Mucosa
Crohn Disease
Mucous Membrane
Reverse Transcriptase Polymerase Chain Reaction
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Serum
C-Reactive Protein
Protein Isoforms
Neutrophils
Fibrosis
Up-Regulation
Biomarkers

Keywords

  • Crohn's disease
  • CXCL1
  • RNA sequencing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

RNA-seq Reveals Transcriptomic Differences in Inflamed and Noninflamed Intestinal Mucosa of Crohn's Disease Patients Compared with Normal Mucosa of Healthy Controls. / Hong, Sung Noh; Joung, Je Gun; Bae, Joon Seol; Lee, Chan Soo; Koo, Ja Seol; Park, Soo Jung; Im, Jong Pil; Kim, You Sun; Kim, Ji Won; Park, Woong Yang; Kim, Young Ho.

In: Inflammatory Bowel Diseases, Vol. 23, No. 7, 01.07.2017, p. 1098-1108.

Research output: Contribution to journalArticle

Hong, Sung Noh ; Joung, Je Gun ; Bae, Joon Seol ; Lee, Chan Soo ; Koo, Ja Seol ; Park, Soo Jung ; Im, Jong Pil ; Kim, You Sun ; Kim, Ji Won ; Park, Woong Yang ; Kim, Young Ho. / RNA-seq Reveals Transcriptomic Differences in Inflamed and Noninflamed Intestinal Mucosa of Crohn's Disease Patients Compared with Normal Mucosa of Healthy Controls. In: Inflammatory Bowel Diseases. 2017 ; Vol. 23, No. 7. pp. 1098-1108.
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abstract = "Background: Aberrant gene expression in the gut mucosa might contribute to the initiation and progression of Crohn's disease (CD). RNA sequencing (RNA-seq) provides precise measurements of expression levels of transcripts and their isoforms. The aim of this study was to use RNA-seq to investigate transcriptomic differences and identify significantly differentially expressed transcripts in inflamed and noninflamed intestinal mucosa of CD patients. Methods: RNA-seq was performed on 13 pairs of inflamed and noninflamed intestinal mucosa from 13 CD patients and on sex-matched normal mucosa of 13 healthy controls. Significantly differentially expressed transcripts were validated by immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction, and enzyme-linked immunosorbent assay. Results: RNA-seq revealed genome-wide transcriptomic differences between normal mucosa, noninflamed, and inflamed CD mucosa. Among 950 differentially expressed genes, 19 were up- or downregulated (upregulation: ANGPT2, CHN1, CPXM1, CPZ, CXCL1, FCN3, GJC1, HSD11B1, LZTS1, MEOX1, MMP12, PLA1A, SERPINE1, SGIP1, and TRPC4; downregulation: FAM189A1, PDE6A, SLC38A4, and HMGCS2) with statistical significance (p < 0.01 and q < 0.05). Among them, CXCL1 exhibited the highest fold change between groups. Immunohistochemistry for CXCL1 revealed no expression in normal mucosa, slightly increased expression in noninflamed CD mucosa, and highly increased expression in inflamed CD mucosa. Quantitative reverse transcriptase polymerase chain reaction showed that CXCL1 expression was significantly associated with epithelial damage, increased infiltration of polymorphonuclear leukocytes, and submucosal fibrosis. Serum CXCL1 concentration measured by enzyme-linked immunosorbent assay was better correlated with CD activity index (r = 0.660) than with C-reactive protein (r = 0.204). Conclusions: RNA-seq revealed transcriptomic differences between normal mucosa, noninflamed CD mucosa, and inflamed CD mucosa. Intestinal and serum CXCL1 was substantially increased with CD activity and can be used as a potential biomarker of CD.",
keywords = "Crohn's disease, CXCL1, RNA sequencing",
author = "Hong, {Sung Noh} and Joung, {Je Gun} and Bae, {Joon Seol} and Lee, {Chan Soo} and Koo, {Ja Seol} and Park, {Soo Jung} and Im, {Jong Pil} and Kim, {You Sun} and Kim, {Ji Won} and Park, {Woong Yang} and Kim, {Young Ho}",
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AU - Hong, Sung Noh

AU - Joung, Je Gun

AU - Bae, Joon Seol

AU - Lee, Chan Soo

AU - Koo, Ja Seol

AU - Park, Soo Jung

AU - Im, Jong Pil

AU - Kim, You Sun

AU - Kim, Ji Won

AU - Park, Woong Yang

AU - Kim, Young Ho

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N2 - Background: Aberrant gene expression in the gut mucosa might contribute to the initiation and progression of Crohn's disease (CD). RNA sequencing (RNA-seq) provides precise measurements of expression levels of transcripts and their isoforms. The aim of this study was to use RNA-seq to investigate transcriptomic differences and identify significantly differentially expressed transcripts in inflamed and noninflamed intestinal mucosa of CD patients. Methods: RNA-seq was performed on 13 pairs of inflamed and noninflamed intestinal mucosa from 13 CD patients and on sex-matched normal mucosa of 13 healthy controls. Significantly differentially expressed transcripts were validated by immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction, and enzyme-linked immunosorbent assay. Results: RNA-seq revealed genome-wide transcriptomic differences between normal mucosa, noninflamed, and inflamed CD mucosa. Among 950 differentially expressed genes, 19 were up- or downregulated (upregulation: ANGPT2, CHN1, CPXM1, CPZ, CXCL1, FCN3, GJC1, HSD11B1, LZTS1, MEOX1, MMP12, PLA1A, SERPINE1, SGIP1, and TRPC4; downregulation: FAM189A1, PDE6A, SLC38A4, and HMGCS2) with statistical significance (p < 0.01 and q < 0.05). Among them, CXCL1 exhibited the highest fold change between groups. Immunohistochemistry for CXCL1 revealed no expression in normal mucosa, slightly increased expression in noninflamed CD mucosa, and highly increased expression in inflamed CD mucosa. Quantitative reverse transcriptase polymerase chain reaction showed that CXCL1 expression was significantly associated with epithelial damage, increased infiltration of polymorphonuclear leukocytes, and submucosal fibrosis. Serum CXCL1 concentration measured by enzyme-linked immunosorbent assay was better correlated with CD activity index (r = 0.660) than with C-reactive protein (r = 0.204). Conclusions: RNA-seq revealed transcriptomic differences between normal mucosa, noninflamed CD mucosa, and inflamed CD mucosa. Intestinal and serum CXCL1 was substantially increased with CD activity and can be used as a potential biomarker of CD.

AB - Background: Aberrant gene expression in the gut mucosa might contribute to the initiation and progression of Crohn's disease (CD). RNA sequencing (RNA-seq) provides precise measurements of expression levels of transcripts and their isoforms. The aim of this study was to use RNA-seq to investigate transcriptomic differences and identify significantly differentially expressed transcripts in inflamed and noninflamed intestinal mucosa of CD patients. Methods: RNA-seq was performed on 13 pairs of inflamed and noninflamed intestinal mucosa from 13 CD patients and on sex-matched normal mucosa of 13 healthy controls. Significantly differentially expressed transcripts were validated by immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction, and enzyme-linked immunosorbent assay. Results: RNA-seq revealed genome-wide transcriptomic differences between normal mucosa, noninflamed, and inflamed CD mucosa. Among 950 differentially expressed genes, 19 were up- or downregulated (upregulation: ANGPT2, CHN1, CPXM1, CPZ, CXCL1, FCN3, GJC1, HSD11B1, LZTS1, MEOX1, MMP12, PLA1A, SERPINE1, SGIP1, and TRPC4; downregulation: FAM189A1, PDE6A, SLC38A4, and HMGCS2) with statistical significance (p < 0.01 and q < 0.05). Among them, CXCL1 exhibited the highest fold change between groups. Immunohistochemistry for CXCL1 revealed no expression in normal mucosa, slightly increased expression in noninflamed CD mucosa, and highly increased expression in inflamed CD mucosa. Quantitative reverse transcriptase polymerase chain reaction showed that CXCL1 expression was significantly associated with epithelial damage, increased infiltration of polymorphonuclear leukocytes, and submucosal fibrosis. Serum CXCL1 concentration measured by enzyme-linked immunosorbent assay was better correlated with CD activity index (r = 0.660) than with C-reactive protein (r = 0.204). Conclusions: RNA-seq revealed transcriptomic differences between normal mucosa, noninflamed CD mucosa, and inflamed CD mucosa. Intestinal and serum CXCL1 was substantially increased with CD activity and can be used as a potential biomarker of CD.

KW - Crohn's disease

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