The hyaluronic acid receptor is induced by stretch injury of rat bladder in vivo and influences smooth muscle cell contraction in vitro

Purpose: Loss of bladder compliance from hypercontractility and fibrosis ma y represent an injury response to excessive intravesical pressure. Together , interactions between cell and extracellular matrix components regulate ce ll response to injury and extracellular matrix remodeling. The receptor for hyaluronic acid mediated motility (RHAMM) is a recently described hyaluron ic acid binding protein known to influence multiple types of cell extracell ular matrix interaction in development, injury and cancer. We evaluate the role of RHAMM in mediating early events in bladder stretch injury. Materials and Methods: An acute stretch injury model was used. The rat blad der was injured by hydrodistention inducing gross hematuria. Tissues were a nalyzed for temporal and spatial expression of RHAMM in the mucosa and detr usor regions by immunostaining, western and reverse transcriptase polymeras e chain reaction analyses. The contractile activity of smooth muscle cell p rimary cultures was analyzed using a gel contraction assay in the presence of peptide fragments known to block RHAMM function. Results: Acute hydrodistention caused immediate and significant injury to t he bladder, with fracturing of smooth muscle cell bundles, edema and hemorr hage. RHAMM immunolocalized to the mucosa and detrusor within 2 hours of in jury, peaking by 5 to 10 hours. A shift from low molecular weight (55 kD.) to high (120 kD.) receptor isoforms was prominent during the peak expressio n period noted by immunolocalization. RHAMM messenger ribonucleic acid incr eased only slightly (40%) by 5 hours after injury. Smooth muscle cell prima ry cultures actively initiated and maintained the contraction of collagen g els by more than 75% of baseline in vitro. Blocking RHAMM function signific antly inhibited the ability to less than 25% of smooth muscle cells to cont ract the gels in vitro. Conclusions: Increased expression of RHAMM is an early event precipitated b y stretch injury to the bladder. Since extracellular matrix hyaluronic acid is found early in tissue repair responses, its receptor RHAMM may be media ting initial bladder responses to stretch injury, some of which (contractio n) may be experimentally blocked in vitro. Since the receptor directly regu lates protein kinase signaling which in turn mediates smooth muscle cell co ntraction and collagen synthesis, further studies of RHAMM function in blad der pathology are warranted.