Preclinical Animal Studies of Intravesical Recombinant Human Proteoglycan 4 as a Novel Potential Therapy for Diseases Resulting From Increased Bladder Permeability.

Autor: Greenwood-Van Meerveld B; Oklahoma Center for Neuroscience, Oklahoma University Health Sciences Center, Oklahoma City, OK; Department of Physiology, Oklahoma University Health Sciences Center, Oklahoma City, OK; Veterans Administration, Oklahoma City, OK., Mohammadi E; Department of Physiology, Oklahoma University Health Sciences Center, Oklahoma City, OK., Latorre R; Oklahoma Center for Neuroscience, Oklahoma University Health Sciences Center, Oklahoma City, OK; Department of Physiology, Oklahoma University Health Sciences Center, Oklahoma City, OK., Truitt ER 3rd; Lubris Biopharma, Framingham, MA., Jay GD; Department of Emergency Medicine, Brown University, Providence, RI., Sullivan BD; Lubris Biopharma, Framingham, MA., Schmidt TA; Biomedical Engineering Department, School of Dental Medicine, University of Connecticut, Farmington, CT., Smith N; Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK., Saunders D; Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK., Ziegler J; Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Biochemistry and Molecular Biology, Oklahoma University Health Sciences Center, Oklahoma City, OK., Lerner M; Department of Surgery, Oklahoma University Health Sciences Center, Oklahoma City, OK., Hurst R; Oklahoma Center for Neuroscience, Oklahoma University Health Sciences Center, Oklahoma City, OK; Department of Biochemistry and Molecular Biology, Oklahoma University Health Sciences Center, Oklahoma City, OK; Department of Urology, Oklahoma University Health Sciences Center, Oklahoma City, OK. Electronic address: robert-hurst@ouhsc.edu., Towner RA; Oklahoma Center for Neuroscience, Oklahoma University Health Sciences Center, Oklahoma City, OK; Department of Physiology, Oklahoma University Health Sciences Center, Oklahoma City, OK; Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK.
Jazyk: angličtina
Zdroj: Urology [Urology] 2018 Jun; Vol. 116, pp. 230.e1-230.e7. Date of Electronic Publication: 2018 Mar 12.
DOI: 10.1016/j.urology.2018.02.034
Abstrakt: Objective: To test in an animal model the hypothesis that recombinant human proteoglycan 4 (rhPRG4; lubricin), a highly O-glycosylated mucin-like glycoprotein, may be a novel surface-active therapeutic for treating bladder permeability with comorbid bowel permeability. Previously we showed that inducing bladder permeability in rats with dilute protamine sulfate (PS) produced colonic permeability and visceral hypersensitivity, suggesting increased bladder permeability could represent an etiologic factor in both interstitial cystitis-bladder pain syndrome and irritable bowel syndrome.
Methods: We used an animal model of catheterized ovariectomized female rats instilled intravesically with 1 mg/mL PS for 10 minutes that after 24 hours were treated with 1.2 mg/mL lubricin or with vehicle alone. After 24 hours the bladder and colon were removed and permeability assessed electrophysiologically with the Ussing chamber to measure the transepithelial electrical resistance. A second set of rats was treated identically, except permeability was assessed on day 3 and on day 5 using contrast-enhanced magnetic resonance imaging with gadolinium diethylenetriamine penta-acetic acid instilled into the bladder.
Results: Intravesical lubricin reversed bladder permeability induced by PS and prevented the concomitant increase in permeability induced in the bowel (organ crosstalk). The protective effect was confirmed with magnetic resonance imaging, and because individual rats could be followed over time, the impermeability of the bladder restored by rhPRG4 remained for 5 days.
Conclusion: These data indicate that instillation of rhPRG4 into a permeable bladder can restore its normally impermeable state, and that the effect lasts for 5 days and also prevents bowel symptoms often comorbid with interstitial cystitis-bladder pain syndrome.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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