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

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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 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.

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Abbreviations

CD44:

Cluster of differentiation 44

ECM:

Extracellular matrix

HA:

Hyaluronic acid

HABP:

Hyaluronan binding protein

HARE:

Hyaluronan receptor for endocytosis

LYVE-1:

Lymphatic vessel endothelial receptor 1

RHAMM:

Receptor for hyaluronan-mediated motility

SIS:

Small intestinal submucosa

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Acknowledgments

This work was supported by a P20 research grant awarded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, 5P20DK097799-02).

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Authors and Affiliations

  1. Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L. Young Blvd., WP3150, Oklahoma City, OK, 73104, USA

    Fadee G. Mondalek, Kar-Ming Fung, Qing Yang, Weijuan Wu, Wenli Lu, Blake W. Palmer, Dominic C. Frimberger, Robert E. Hurst, Bradley P. Kropp & Huesh-Kung Lin

  2. Department of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, OK, 73019, USA

    Fadee G. Mondalek

  3. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Kar-Ming Fung & Huesh-Kung Lin

  4. Oklahoma City Department of Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA

    Kar-Ming Fung & Beverley Greenwood-Van Meerveld

  5. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Weijuan Wu & Beverley Greenwood-Van Meerveld

  6. Department of Pediatrics, Shanghai Ruijin Hospital, Medical School of Shanghai Jiao Tong University, Shanghai, 200025, China

    Wenli Lu

  7. Oklahoma Center for Neuroscience, Oklahoma City, OK, 73104, USA

    Beverley Greenwood-Van Meerveld

  8. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Robert E. Hurst

Authors
  1. Fadee G. Mondalek
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  2. Kar-Ming Fung
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  3. Qing Yang
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  4. Weijuan Wu
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  5. Wenli Lu
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  6. Blake W. Palmer
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  8. Beverley Greenwood-Van Meerveld
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  9. Robert E. Hurst
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  10. Bradley P. Kropp
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  11. Huesh-Kung Lin
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Corresponding author

Correspondence to Huesh-Kung Lin.

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Mondalek, F.G., Fung, KM., Yang, Q. et al. Temporal expression of hyaluronic acid and hyaluronic acid receptors in a porcine small intestinal submucosa-augmented rat bladder regeneration model. World J Urol 33, 1119–1128 (2015). https://doi.org/10.1007/s00345-014-1403-5

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  • DOI: https://doi.org/10.1007/s00345-014-1403-5

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