The relaxin gene knockout mouse: a model of progressive scleroderma.
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 The increased collagen was observed primarily in the dermis of RLX-/- mice by 1 mo of age, and eventually superseded the hypodermal layer.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.
Samuel
Chrishan S
CS
Relaxin Group, Howard Florey Institute of Experimental Physiology & Medicine, The University of Melbourne, Victoria, Australia. c.samuel@hfi.unimelb.edu.au
Zhao
Chongxin
C
Yang
Qing
Q
Wang
Hong
H
Tian
Hongsheng
H
Tregear
Geoffrey W
GW
Amento
Edward P
EP
D000818:Animals; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012065:Relaxin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D045743:Scleroderma, Diffuse / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000737:chemistry / Q000473:pathology
D012065:Relaxin; D003094:Collagen