Alveolar CCN1 is associated with mechanical stretch and acute respiratory distress syndrome severity

Am J Physiol Lung Cell Mol Physiol. 2020 Nov 1;319(5):L825-L832. doi: 10.1152/ajplung.00073.2020. Epub 2020 Sep 16.


The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses, including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury, and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI), 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch, and 3) CCN1 in BALF from mechanically ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI (n = 6) versus noninjured controls (n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS (n = 77) had higher BALF CCN1 levels compared with mechanically ventilated subjects without ARDS (n = 45) (P < 0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse [Formula: see text]/[Formula: see text] ratios (all P < 0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury, and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.

Keywords: CCN1; acute lung injury; acute respiratory distress syndrome.

Publication types

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

MeSH terms

  • Acute Lung Injury / metabolism
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cysteine-Rich Protein 61 / metabolism*
  • Inflammation / metabolism
  • Lung / metabolism
  • Mice
  • Respiration, Artificial* / methods
  • Respiratory Distress Syndrome / metabolism*
  • Ventilator-Induced Lung Injury / metabolism*


  • CCN1 protein, mouse
  • Cysteine-Rich Protein 61