Transcriptomic signature of gut microbiome-contacting cells in colon of spontaneously hypertensive rats

Physiol Genomics. 2020 Mar 1;52(3):121-132. doi: 10.1152/physiolgenomics.00087.2019. Epub 2019 Dec 23.

Abstract

Fecal matter transfer from hypertensive patients and animals into normotensive animals increases blood pressure, strengthening the evidence for gut-microbiota interactions in the control of blood pressure. However, cellular and molecular events involved in gut dysbiosis-associated hypertension remain poorly understood. Therefore, our objective in this study was to use gene expression profiling to characterize the gut epithelium layer in the colon in hypertension. We observed significant suppression of components of T cell receptor (TCR) signaling in the colonic epithelium of spontaneously hypertensive rats (SHR) when compared with Wistar Kyoto (WKY) normotensive rats. Western blot analysis confirmed lower expression of key proteins including T cell surface glycoprotein CD3 gamma chain (Cd3g) and lymphocyte cytosolic protein 2 (Lcp2). Furthermore, lower expression of cytokines and receptors responsible for lymphocyte proliferation, differentiation, and activation (e.g., Il12r, Il15ra, Il7, Il16, Tgfb1) was observed in the colonic epithelium of the SHR. Finally, Alpi and its product, intestinal alkaline phosphatase, primarily localized in the epithelial cells, were profoundly lower in the SHR. These observations demonstrate that the colonic epithelium undergoes functional changes linked to altered immune, barrier function, and dysbiosis in hypertension.

Keywords: TCR signaling pathway; colonic epithelium; gene expression profile; hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Alkaline Phosphatase / metabolism
  • Animals
  • Blood Pressure
  • CD3 Complex / metabolism
  • Colon / metabolism*
  • Cytokines / metabolism
  • Dysbiosis
  • Gastrointestinal Microbiome / genetics*
  • Hypertension / metabolism*
  • Intestinal Mucosa / metabolism*
  • Isoenzymes / metabolism
  • Male
  • Phosphoproteins / metabolism
  • RNA-Seq
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Antigen, T-Cell / metabolism
  • Transcriptome*

Substances

  • Adaptor Proteins, Signal Transducing
  • CD3 Complex
  • CD3 antigen, gamma chain
  • Cytokines
  • Isoenzymes
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • SLP-76 signal Transducing adaptor proteins
  • Alpi protein, rat
  • Alkaline Phosphatase