title: Temporal expression of hyaluronic acid and hyaluronic acid receptors in a porcine small intestinal submucosa-augmented rat bladder regeneration model.
abstract: BACKGROUND
  Hyaluronic acid (HA), a non-sulfated glycosaminoglycan, is an essential component of the extracellular matrix (ECM). Since HA is involved in many phases of wound healing and may play a key role in tissue repair and regeneration, this study was intended to understand temporal and spatial expression of HA and HA receptors (HARs) during the course of bladder regeneration in rats.
  
  
  METHODS
  Sprague-Dawley rats were subjected to partial cystectomy followed by augmentation with porcine small intestinal submucosal (SIS) prepared from distal sections of the small intestine. SIS-augmented bladders were harvested between postoperative days 2 and 56.
  
  
  RESULTS
  Bladder regeneration proceeded without complications. All augmented bladders had complete urothelial lining and smooth muscle bundles by day 56 post-augmentation. Temporal and spatial distributions of HA and HARs were studied by immunohistochemistry in regenerating bladders. The strongest HA immunoreactivity was observed in the ECM on postoperative days 28 and 56. Cluster of differentiation 44 (CD44) immunoreactivity was detected in the cytoplasm of urothelial cells on day 56; and LYVE-1 immunoreactivity was exclusively limited to lymphatic vessels on days 28 and 56.
  
  
  CONCLUSIONS
  We demonstrated that HA was synthesized throughout the course of bladder wound healing and regeneration; and HA deposition coincided with urothelial differentiation. Expression of CD44 and LYVE-1 followed the same temporal pattern as HA deposition. Therapeutic modalities through local delivery of exogenous HA to improve the outcome of SIS-mediated bladder regeneration might need to be coordinated with HAR expression in order to achieve maximal regenerative responses as opposed to fibrosis.
authors.affiliation: Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L. Young Blvd., WP3150, Oklahoma City, OK, 73104, USA.
authors.forename: Fadee G
authors.initials: FG
authors.lastname: Mondalek
authors.forename: Kar-Ming
authors.initials: KM
authors.lastname: Fung
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Weijuan
authors.initials: W
authors.lastname: Wu
authors.forename: Wenli
authors.initials: W
authors.lastname: Lu
authors.forename: Blake W
authors.initials: BW
authors.lastname: Palmer
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Frimberger
authors.forename: Beverley
authors.initials: B
authors.lastname: Greenwood-Van Meerveld
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hurst
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Kropp
authors.forename: Huesh-Kung
authors.initials: HK
authors.lastname: Lin
mesh_terms: D000818:Animals; D015653:Cystectomy; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000473:pathology / Q000637:transplantation; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D062326:Re-Epithelialization / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012038:Regeneration / Q000235:genetics; D013552:Swine; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C533408:Lyve1 protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C472814:hyaluronan receptor 175-kDa, rat; C098946:hyaluronan-mediated motility receptor; D006820:Hyaluronic Acid