HUMAN RELAXIN DECREASES COLLAGEN ACCUMULATION IN-VIVO IN 2 RODENT MODELS OF FIBROSIS

The reproductive hormone, relaxin, inhibits collagen synthesis in vitr o by normal human dermal fibroblasts. In the present study, recombinan t human relaxin is shown to modulate collagen accumulation and organiz ation by mesenchymal cells in vivo in two rodent models of fibrosis: 1 ) fibrotic infiltration of polyvinyl alcohol sponge implants in rats, and 2) capsule formation around implanted osmotic pumps in mice. In th e sponge, relaxin inhibits collagen accumulation, as measured by hydro xyproline content, in a dose-responsive manner by up to 25-29% in anim als receiving 30 ng/ml relaxin, a finding supported by a decrease in c ollagen-specific trichrome staining in sections of sponges from relaxi n-treated animals. In mice, the capsules surrounding relaxin-containin g pumps are thinner and less dense than are capsules from control pump s. Ultrastructurally, control capsules are composed of densely packed parallel arrays of collagen fibrils, whereas fibrils more frequently a re not packed in parallel arrays and are less abundant in treated caps ules.