Dlx1 and Rgs5 in the ductus arteriosus: vessel-specific genes identified by transcriptional profiling of laser-capture microdissected endothelial and smooth muscle cells

PLoS One. 2014 Jan 28;9(1):e86892. doi: 10.1371/journal.pone.0086892. eCollection 2014.

Abstract

Closure of the ductus arteriosus (DA) is a crucial step in the transition from fetal to postnatal life. Patent DA is one of the most common cardiovascular anomalies in children with significant clinical consequences especially in premature infants. We aimed to identify genes that specify the DA in the fetus and differentiate it from the aorta. Comparative microarray analysis of laser-captured microdissected endothelial (ECs) and vascular smooth muscle cells (SMCs) from the DA and aorta of fetal rats (embryonic day 18 and 21) identified vessel-specific transcriptional profiles. We found a strong age-dependency of gene expression. Among the genes that were upregulated in the DA the regulator of the G-protein coupled receptor 5 (Rgs5) and the transcription factor distal-less homeobox 1 (Dlx1) exhibited the highest and most significant level of differential expression. The aorta showed a significant preferential expression of the Purkinje cell protein 4 (Pcp4) gene. The results of the microarray analysis were validated by real-time quantitative PCR and immunohistochemistry. Our study confirms vessel-specific transcriptional profiles in ECs and SMCs of rat DA and aorta. Rgs5 and Dlx1 represent novel molecular targets for the regulation of DA maturation and closure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ductus Arteriosus / metabolism*
  • Endothelial Cells / metabolism*
  • Female
  • Gene Expression Profiling*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Laser Capture Microdissection*
  • Myocytes, Smooth Muscle / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity / genetics
  • RGS Proteins / genetics*
  • RGS Proteins / metabolism
  • Rats, Wistar
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • RGS Proteins
  • Rgs5 protein, rat
  • Transcription Factors

Grant support

This work was supported by the Madeleine Schickedanz-KinderKrebs-Stiftung. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.