Relaxin deficiency in mice is associated with an age-related progression of pulmonary fibrosis.
Relaxin (RLX) is a peptide hormone with known antifibrotic properties. However, its significance in the lung and its role as a therapeutic agent against diseases characterized by pulmonary fibrosis are yet to be established. In this study, we examined age-related structural and functional changes in the lung of relaxin-deficient mice. Lung tissues of male and female RLX knockout (-/-) and RLX wild-type (+/+) mice at various ages were analyzed for changes in collagen expression and content. We demonstrate an age-related progression of lung fibrosis in RLX -/- mice with significantly increased tissue wet weight, collagen content and concentration, alveolar congestion, and bronchiole epithelium thickening. The increased fibrosis was associated with significantly altered peak expiratory flow and lung recoil (lung function) in RLX -/- mice. Treatment of RLX -/- mice with relaxin in early and developed stages of fibrosis resulted in the reversal of collagen deposition. Organ bath studies showed that precontracted lung strips relaxed in the presence of relaxin. Together, these data indicate that relaxin may provide a means to regulate excessive collagen deposition in diseased states characterized by pulmonary fibrosis.
Samuel
Chrishan S
CS
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Victoria, Australia. : c.samuel@hfi.unimelb.edu.au
Zhao
Chongxin
C
Bathgate
Ross A D
RA
Bond
Courtney P
CP
Burton
Matthew D
MD
Parry
Laura J
LJ
Summers
Roger J
RJ
Tang
Mimi L K
ML
Amento
Edward P
EP
Tregear
Geoffrey W
GW
D000375:Aging; D000818:Animals; D003094:Collagen / Q000032:analysis; D018450:Disease Progression; D005260:Female; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009929:Organ Size; D011650:Pulmonary Alveoli / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000235:genetics; D012065:Relaxin / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use
D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D012065:Relaxin; D003094:Collagen