Gene expression profiles during tissue remodeling following bladder outlet obstruction

Sci Rep. 2021 Jun 23;11(1):13171. doi: 10.1038/s41598-021-92756-1.

Abstract

Bladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased bladder smooth muscle proportion and HIF1α mRNA levels compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (DBP), were upregulated only in the mild muscular hypertrophy group. DBP expression levels were increased in bladder smooth muscle cells in response to hypoxic stress. DBP associated with enhancer and promoter regions of NOS3 gene locus and upregulated NOS3 gene expression under hypoxic conditions. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian clock components might be involved in control of urinary function via transcriptional gene regulation in response to hypoxic stimuli.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia
  • Cells, Cultured
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Hypertrophy
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Nitric Oxide Synthase Type III / biosynthesis
  • Nitric Oxide Synthase Type III / genetics
  • RNA-Seq
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Urinary Bladder Neck Obstruction / genetics*
  • Urinary Bladder Neck Obstruction / metabolism

Substances

  • DBP protein, human
  • DBP protein, rat
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transcription Factors
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat