Collagen triple helix repeat containing 1, a novel secreted protein in injured and diseased arteries, inhibits collagen expression and promotes cell migration.

Collagen triple helix repeat containing 1 (Cthrc1) was identified in a screen for differentially expressed sequences in balloon-injured versus normal arteries. Cthrc1 expression was not detectable in normal arteries. However, on injury it was transiently expressed by fibroblasts of the remodeling adventitia and by smooth muscle cells of the neointima. It was also found in the matrix of calcifying human atherosclerotic plaques. CTHRC1 is a secreted 28-kDa protein that is glycosylated and highly conserved from lower chordates to mammals. A short collagen motif with 12 Gly-X-Y repeats appears to be responsible for trimerization of the protein and this renders the molecule susceptible to cleavage by collagenase. Cthrc1 mRNA expression levels are increased in response to transforming growth factor-beta and bone morphogenetic protein-4. Cell migration assays performed with CTHRC1-overexpressing fibroblasts and smooth muscle cells demonstrate that increased CTHRC1 levels are associated with enhanced migratory ability. Furthermore, CTHRC1 overexpression caused a dramatic reduction in collagen type I mRNA and protein levels. Our data indicate that the novel molecule CTHRC1 is transiently expressed in the arterial wall in response to injury where it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration.

Scaling of the fast-start escape response of juvenile bluegills.

Morphology, size and physiological properties change markedly across fish ontogeny. This impacts locomotor performance and organismal fitness, although the effects are unpredictable due to the complexity of phenotype-function relationships. Morphological and behavioral changes with growth are often paralleled by changes in habitat use, diet and vulnerability to predators. Our goal was to quantify the changes in external morphology and escape performance throughout post-larval development in bluegill sunfish (Lepomis macrochirus), and place these changes in context with known changes in habitat use in the field. Development into adult ecomorphs is associated with phenotypic plasticity in response to habitat-specific differences in diet. On this basis, we hypothesized that variation in morphology and performance would increase during bluegill ontogeny as diversification of adult ecomorphs occurred. However, we found that variation in phenotype and escape performance decreased during early ontogeny. Phenotypic variation expanded later in development, after fish gained access to the variety of habitats and food types that may favor phenotypic plasticity. Performance is predicted to decline with growth due to the differential scaling of inertia and cross-sectional area, a major determinant of muscle force. In contrast, acceleration increased with size, and velocity and acceleration increased more rapidly with size than predicted. Post-larval maturation in bluegill featured a shift to a deeper body shape, and an increase in the relative size of the anal and caudal fins. This was a likely factor in the deviation of escape performance scaling relationships from predictions based on geometric similarity.