Abstract
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
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
