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RHAMM alters smooth muscle cell (SMC) remodeling of collagen‐hyaluronan (HA) matrix
Author(s) -
MA XUE,
BERNISH BRIAN,
GEARY RANDOLPH
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb332
Subject(s) - chemistry , extracellular matrix , contraction (grammar) , microbiology and biotechnology , hyaluronic acid , cd44 , wound healing , focal adhesion , cell migration , cell adhesion , receptor , in vitro , cell , immunology , biochemistry , anatomy , endocrinology , biology
HA is prominent in ECM at sites of artery injury and alters SMC proliferation and migration by binding receptors CD44 and RHAMM, respectively. HA also enhances contraction of collagen by SMC in vitro but the molecular regulation of this effect is ill defined. Given HA binding of RHAMM induces migration we hypothesize RHAMM also mediates HA‐induced collagen remodeling. To test this hypothesis, rat SMC were pre‐treated with blocking antibody and effects on adhesion, migration, collagen gel contraction determined. Consistent with the literature, HA promoted migration via RHAMM, as blocking antibody inhibited healing of a scratch assay by 84% compared to IgG control (%healing, 48 hr: 8±2 vs 92±2 %, respectively, p=0.008) but without significant effect on initial SMC adhesion to collagen‐coated plates(p=0.08). HA enhanced contraction of collagen‐I gels and contraction was further increased by RHAMM blockade (gel diam, 18hr: 8.5±0.15 vs 5.5±0.1, p=0.01). Gel histology showed increased pericellular collagen with RHAMM blockade (156±7% of control, p<0.05) and reduced cell speading (p=0.015). In summary, RHAMM promoted SMC migration with little effect on initial adhesion. Blocking RHAMM enhanced HA‐induced collagen gel contraction, suggesting RHAMM plays an inhibitory role in collagen remodeling, making RHAMM a potential target for treating constrictive remodeling in vivo . Research Support: NIH R01HL57557