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Impaired T Cell Receptor (TCR) Signaling in the Intestinal Epithelium of Spontaneously Hypertensive Rats
Author(s) -
Yang Tao,
Goel Ruby,
Richards Elaine K,
Raizada Mohan K
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.595.2
Subject(s) - biology , epithelium , epigenetics , intestinal epithelium , flow cytometry , gut flora , receptor , endocrinology , immunology , microbiology and biotechnology , medicine , gene , genetics
Objective Evidence indicates that altered gut microbiota is associated with hypertension implicating an impaired host‐microbiome cross‐talk in the pathophysiology of this disease. Although gut epithelium is the key host organelle in the host‐microbiota communication, little is known about the role of these cells in altered gut microbiota in hypertension. Given that gut micorbiota has profound effects on epigenetic regulation, our present study was to investigate the hypothesis that gut epithelium from hypertension exhibits unique gene and epigenetic profiles, associated with changes in biological functions. Methods Epithelium from proximal colon of 16 weeks old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used for RNA‐seq. Western blotting was performed to validate changes in the mRNAs and flow cytometry was used to analyze the intraepithelial cell (IEL) populations related to the aforementioned changes of mRNA and proteins. Biological pathway analysis was conducted to determine functional differences between WKY and SHR epithelium. Reduced‐representation bisulfite sequencing was used to study the methylation pattern changes associated with the changes found by RNA‐seq. Results RNA‐seq study demonstrated global suppression of gene expression in the SHR epithelium, especially for the genes related to TCR signaling pathway at both translational (e.g. CD3g –76.9%; Lat −74.6%; Lcp2 −70%, Two‐way ANOVA, N=4/strain, P<0.0001) and posttranslational levels (e.g. CD3g −69.2%; Lat −33.6%; Lcp2 −57%, Two‐way ANOVA, N=4/strain, P=0.011). Importantly, these changes were not attributed to the differences in IEL numbers between WKY and SHR, indicating an intrinsic difference in characteristic of the IEL. Prediction of biological processes of epithelium revealed significant enrichment in immune regulatory mechanism in the WKY, in contrast to immune responses to bacteria in SHR. In addition, significant elevation in global methylation was demonstrated in the SHR epithelium (+53.2%, N=4/strain, P=0.0478). Conclusion Our data demonstrated suppression of immune regulatory mechanism (e.g. TCR signalingrelated components) and increase of methylation at the interface of gut microbiota and epithelium on the host side, which suggest that host epithelium could a potential therapeutic target in addition to the gut dysbiosis in hypertension. Support or Funding Information NIHLBI 5R01HL132448‐03 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .