The senescence-associated matricellular protein CCN1 in plasma of human subjects with idiopathic pulmonary fibrosis

Respir Med. 2020 Jan:161:105821. doi: 10.1016/j.rmed.2019.105821. Epub 2019 Nov 19.

Abstract

Introduction: Cellular senescence has been linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF). CCN1 is a matricellular protein that has been shown to induce cellular senescence and contribute to lung fibrosis in pre-clinical models. In this report, we determined plasma CCN1 levels in patients with IPF and its potential role in clinical outcomes.

Methods and results: We evaluated 88 patients diagnosed with IPF at the University of Alabama at Birmingham. CCN1 levels were measured in plasma specimens by ELISA. The primary outcome measure was transplant-free survival (TFS) duration. High-CCN1 levels were associated with a lower transplant-free survival independent of %FVC and %DLCO compared to patients with low plasma CCN1 (HR = 2.15; 95%CI 1.04-4.45, p = 0.04).

Conclusion: This study demonstrates that plasma levels of CCN1 may be predictive of survival in IPF. Given the plausible role of CCN1 in cellular senescence and pathobiology of IPF, the predictive value of CCN1 in disease progression among patients with IPF warrants further investigation.

Keywords: CCN1; Cellular senescence; Idiopathic pulmonary fibrosis; Transplant-free survival.

Publication types

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

MeSH terms

  • Aged
  • Cellular Senescence*
  • Cysteine-Rich Protein 61 / blood*
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / blood*
  • Idiopathic Pulmonary Fibrosis / etiology*
  • Idiopathic Pulmonary Fibrosis / mortality
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Predictive Value of Tests
  • Survival Rate

Substances

  • CCN1 protein, human
  • Cysteine-Rich Protein 61