Relaxin is a
peptide hormone with anti-fibrotic properties. To investigate the long-term effects of
relaxin deficiency on the ageing skin, we compared structural changes in the skin of ageing
relaxin-deficient (RLX-/-) and normal (RLX+/+) mice, by biochemical, histological, and magnetic resonance imaging analyses. Skin biopsies from RLX+/+ and RLX-/- mice were obtained at different ages and analyzed for changes in
collagen expression and distribution. We demonstrated an age-related progression of dermal
fibrosis and thickening in male and female RLX-/- mice, associated with marked increases in types I and III
collagen. The increased
collagen was observed primarily in the dermis of RLX-/- mice by 1 mo of age, and eventually superseded the hypodermal layer. Additionally, fibroblasts from the dermis of RLX-/- mice were shown to produce increased
collagen in vitro. Recombinant human gene-2 (H2)
relaxin treatment of RLX-/- mice resulted in the complete reversal of dermal
fibrosis, when applied to the early onset of disease, but was ineffective when applied to more established stages of dermal
scarring. These combined findings demonstrate that
relaxin provides a means to regulate excessive
collagen deposition in disease states characterized by dermal
fibrosis and with our previously published work demonstrate the
relaxin-null mouse as a model of
progressive scleroderma.