Decreased expression of P54(nrb) /NonO correlates with collagen deposition and fibrosis in human aortic dissection

Histopathology. 2014 Oct;65(4):570-80. doi: 10.1111/his.12434. Epub 2014 Aug 1.

Abstract

Aims: Aortic dissection (AD) is characterized by changes in the extracellular matrix, including fibrosis with collagen production. P54(nrb) /NonO is known to be involved in collagen formation. In this study, we examined whether AD is associated with abnormal P54(nrb) /NonO expression.

Methods and results: Aortic specimens and serum were obtained from 10 patients with AD and 10 controls. In-vitro cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts (AFs) were obtained from organ donors. P54(nrb) /NonO protein and mRNA levels were determined by Western blot, immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (quantitative real-time RT-PCR). To evaluate collagen expression, we stained tissue sections with Masson's trichrome. Serum concentration of TNF-α was determined by enzyme-linked immunosorbent assay (ELISA). Aortic P54(nrb) /NonO protein and mRNA were decreased in AD patients, compared with controls. Decreased P54(nrb) /NonO mRNA correlated significantly with increased collagen deposition and fibrosis in AD aortas. In VSMCs and AFs from normal human aortas, P54(nrb) /NonO was expressed strongly and localized to the nucleus.

Conclusions: Patients with AD exhibited significantly decreased expression of P54(nrb) /NonO. The significant correlation between P54(nrb) /NonO and collagen may point to novel thinking about collagen metabolism research in AD aorta.

Keywords: P54nrb/NonO; aortic dissection; collagen; fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aortic Diseases / metabolism*
  • Aortic Diseases / pathology*
  • Collagen / metabolism*
  • DNA-Binding Proteins
  • Female
  • Fibrosis
  • Humans
  • Male
  • Middle Aged
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Octamer Transcription Factors / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • DNA-Binding Proteins
  • NONO protein, human
  • Nuclear Matrix-Associated Proteins
  • Octamer Transcription Factors
  • RNA, Messenger
  • RNA-Binding Proteins
  • Tumor Necrosis Factor-alpha
  • Collagen