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J Neurogastroenterol Motil. 2020;26(2):248-258.

Expression of Tight Junction Proteins According to Functional Dyspepsia Subtype and Sex.

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제1저자 이주엽 · 교신저자 김나영

소속 (5)
  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.
  2. Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
  3. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  4. Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, District of Columbia, USA.
  5. Department of Medicine, Meharry Medical Center, Nashville, Tennessee, USA.

Abstract

BACKGROUND/AIMS To determine whether the expression of tight junction proteins (TJPs) differs depending on the subtype of functional dyspepsia (FD) and sex.

METHODS Control (n = 95) and FD (n = 165) groups based on Rome III criteria were prospectively enrolled. Gastric mucosal mRNA expression levels of various TJPs (claudins [CLDN] 1, 2, and 4; zonula occludens-1; occludin [OCLN]) were assessed by reverse transcription polymerase chain reaction. Western blot was performed to determine the levels of various TJPs. Helicobacter pylori infection status was evaluated by histology, rapid urease test, and culture. Questionnaires were analyzed.

RESULTS In all groups irrespective of H. pylori , FD group showed significantly higher CLDN2 mRNA levels than control group (P = 0.048). The level of CLDN4 mRNA expression was significantly lower in female FD group than in male FD group (P = 0.018). In H. pylori uninfected subjects, the level of CLDN1 mRNA expression in female FD group was significantly lower than that of male FD group (P = 0.014). The level of CLDN2 mRNA expression was significantly higher in the male postprandial distress syndrome (P = 0.001) and male epigastric pain syndrome (P = 0.023) groups than in the male control group. In Western blot analysis, the expression of OCLN was significantly elevated 48 hour after the culture with H. pylori strain 43504.

CONCLUSIONS H. pylori can affect a variety of TJPs, particularly claudin-4 and occludin. Claudin-2 is thought to be involved in FD irrespective of H. pylori status, especially in the pathophysiology of male FD.

Keywords

Claudin-2DyspepsiaHelicobacter pyloriOccludinTight junction proteins

Figures

Figure 1
Figure 1 Comparison of tight junction protein mRNA expression levels in the control and functional dyspepsia (FD) groups in all groups irrespective of Helicobacter pylori status. (A-C) Claudin-2 (CLDN2), CLDN4, and occludin (OCLN) mRNA expression were higher in male FD group than those of control group (P = 0.017, 0.054, and 0.044, respectively). (D-F) There were no significant differences in CLDN2, CLDN4, and OCLN mRNA expression level between female FD group and female control group. Data are expressed as median (interquartile range).
Figure 2
Figure 2 Comparison of tight junction protein mRNA expression levels in the control and functional dyspepsia (FD) groups in Helicobacter pylori-uninfected subjects. (A-C) Only claudin-2 (CLDN2) mRNA expression was significantly higher in male FD group than that of control group (P = 0.006). (D-F) There were no significant differences in CLDN2, CLDN4, and occludin (OCLN) mRNA expression level between female FD group and female control group. Data are expressed as median (interquartile range).
Figure 3
Figure 3 Comparison of claudin-2 (CLDN2) mRNA expression levels according to functional dyspepsia subtypes in male Helicobacter pylori uninfected subjects. The level of CLDN2 mRNA expression was significantly higher in postprandial distress syndrome (PDS) group than that of control group (P = 0.001) and the level of CLDN2 mRNA expression was significantly higher in epigastric pain syndrome (EPS) group than that of control group (P = 0.023). Data are expressed as median (interquartile range).
Figure 4
Figure 4 Expression of zonula occludens-1 (ZO-1), occludin (OCLN), and claudin-2 (CLDN2) in HFE 145 cell lines after cultured with Helicobacter pylori 43504 strain (HP ATCC 43504; O4 strain). (A) Western blot analysis of ZO-1, OCLN, and CLDN2. (B, D) There were no significant differences in the expression of ZO-1 and CLDN2 between control and H. pylori infection group. (C) The expression of OCLN was significantly elevated 48 hours after the culture with H. pylori strain 43504. Data are expressed as means ± SE for 3 experiments. *P < 0.05 significantly different from the control.

그림 출처: PubMed Central 공개 논문 (PMC7176499)

Conflict of interest statement

Conflicts of interest: None.

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Journal Article
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Journal of neurogastroenterology and motility · ISSN 2093-0879
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