Temporal expression of hyaluronic acid and hyaluronic acid receptors in a porcine small intestinal submucosa-augmented rat bladder regeneration model

Abstract

Introduction 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. Materials and 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 post-operative 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 post-operative days 28 and 56. 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.

Characterization of Plasma Membrane Localization and Phosphorylation Status of Organic Anion Transporting Polypeptide (OATP) 1B1 c.521 T>C Nonsynonymous Single-Nucleotide Polymorphism

“…The IHC staining was conducted by the OUHSC Stephenson Cancer Center Tissue Pathology Shared Resource facilities using a method similar to published previously (25,30,31). The immunohistochemistry protocol was based on the manufacturer's protocol for the Leica Bond-III™ Polymer Refine Detection system (DS 98000).…”

The Role of CD44 in Disease Pathophysiology and Targeted Treatment

“…A recent study in a rat bladder regeneration model found that HA deposition in a regenerating bladder after partial cystectomy was required for proper wound healing ( 48 ). CD44 expression also increased as the wound healed, mimicking the deposition pattern of HA.…”

Low-Intensity Extracorporeal Shock Wave Therapy Promotes Bladder Regeneration and Improves Overactive Bladder Induced by Ovarian Hormone Deficiency from Rat Animal Model to Human Clinical Trial

“…Previous studies have implicated that HA was involved in wound healing and tissue regeneration, and endothelial cell proliferation, as well as angiogenesis. HA interacted with HA receptors, including the cluster of CD44, receptor for HA-mediated motility (RHAMM), and Toll-like receptor-4 (TLR-4) to regulate urothelial cell proliferation, differentiation, and migration [63,64]. Transgenic mice with the expression of an antisense CD44 cDNA under the control of the keratin-5 promoter exhibited defective keratinocyte proliferation, indicating that HA receptor CD44 played an important role in the regulation of keratinocyte proliferation in response to extracellular stimuli [65].…”