Incidence of Pulmonary Fibrosis in Lungs of CUX‐1 Transgenic Mice

Abstract

CUX‐1 is a transcriptional repressor gene and part of the network controlling G1‐S phase transition by repressing the cyclin‐kinase inhibitors p21 and p27. CUX‐1 transgenic mice develop polycystic kidneys, reduced spermatogenesis, and liver fibrosis as a consequence of aberrant repression of p27. We reported that these mice also show severe pulmonary inflammation with vasculitis, bronchitis, bronchiectasis, and diffuse presence of fibroblasts.This study reports the presence of collagen using Image J software (NIH program) on slides of lungs of CUX‐1 mice stained by trichrome. Wild type mice were used as controls. An average of seven photographs at 400x magnification were taken on the lungs of each mouse.Collagen presence and intensity was 17.06% in lungs of CUX‐1 mice versus 8.73% the wild type mice (p<0.05). Fibrosis was mostly evident in the basal membrane and musculature of the ectasic bronchi and the peribronchial arteries. CUX‐1 mice also showed medial thickening, reduced lumen patency (64% versus 76% in wild type, p 0.015), and reduced media/adventitia ratio (42% versus 64% in wild type, p 0.018). Fibroblasts were particularly evident in the adventitia. Data using a specific rat stain for SMA‐1 confirm those ones observed with trichrome.Our data quantitatively confirms the presence of severe pulmonary fibrosis in these mice. Would some patients with polycystic kidney disease also have aberrant repression of p21 and p27 and develop pulmonary fibrosis?