Alterations in the Molecular Determinants of Bladder Compliance at Hydrostatic Pressures less than 40 cm. H ₂ O

Abstract

No AccessJournal of UrologyPEDIATRIC UROLOGY1 Dec 2002Alterations in the Molecular Determinants of Bladder Compliance at Hydrostatic Pressures less than 40 cm. H2O BJÖRN O. BACKHAUS, MARTIN KAEFER, KAREN M. HABERSTROH, KAREN HILE, JIRO NAGATOMI, RICHARD C. RINK, MARK P. CAIN, ANTHONY CASALE, and RENA BIZIOS BJÖRN O. BACKHAUSBJÖRN O. BACKHAUS More articles by this author , MARTIN KAEFERMARTIN KAEFER Financial interest and/or other relationship with Alza and Pharmacia. More articles by this author , KAREN M. HABERSTROHKAREN M. HABERSTROH More articles by this author , KAREN HILEKAREN HILE More articles by this author , JIRO NAGATOMIJIRO NAGATOMI More articles by this author , RICHARD C. RINKRICHARD C. RINK Financial interest and/or other relationship with Alza, Bayer and Qmed. More articles by this author , MARK P. CAINMARK P. CAIN Financial interest and/or other relationship with Aventis and Pharmacia. More articles by this author , ANTHONY CASALEANTHONY CASALE Financial interest and/or other relationship with Aventis-Pasteur, Bayer and Pharmacia. More articles by this author , and RENA BIZIOSRENA BIZIOS More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64226-7AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Bladder outlet obstruction with intravesical pressures exceeding 40 cm. H2O often results in irreversible renal damage. Bladder outlet obstruction also results in alterations in bladder physiology, including wall thickening, reduced compliance and decreased capacity. If unchecked these changes may lead to the subsequent need for bladder augmentation. From a biomechanical standpoint, compliance is primarily related to extracellular matrix deposition, which in turn is dependent on the balanced activity of proteolytic enzymes (that is matrix metalloproteinases [MMPs]) and their endogenous inhibitors (that is tissue inhibitors of metalloproteinases [TIMPs]). To date, the threshold pressure above which alterations in these key determinants of bladder compliance occur has not been determined. Therefore, using a novel device of our own design, we applied hydrostatic pressures in the physiological range to human bladder smooth muscle cells to determine the effect on MMPs, TIMP-1 and transcription of the major structural collagens (types I and III). Materials and Methods: Human bladder smooth muscle cells (staining positive for α-smooth muscle actin) were plated at a density of 100,000 cells per 10 cm.2 and cultured for 2 days in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum. Cells were subsequently exposed to pressures of 0.3, 20 and 40 cm. H2O for 1, 3, 7 and 24 hours in serum-free DMEM. A computer interface maintained pressure levels for the duration of the experiments and collected pressure data. MMP-1 and 3, and TIMP-1 immunoassay and zymography for MMP-2 and 9 were performed. Polymerase chain reaction for human collagen types I and III was performed following reverse transcription of total purified mRNA. All experiments were repeated 3 times and statistical analysis was performed using a 2-tailed Student t test. Results: Exposure of bladder smooth muscle cells to a sustained hydrostatic pressure of 20 cm. H2O for 7 hours in serum-free DMEM resulted in a time dependent decrease in MMP-1, 2 and 9 activity (15%, 37% and 25%) compared to controls maintained at atmospheric pressure (p <0.01). TIMP-1 levels increased an average of 10% after exposure to 20 cm. H2O. These changes became statistically significant when the cells were exposed to 40 cm. H2O pressure for 3, 7 and 24 hours (+14%, +21% and +50%, respectively). No statistically significant differences in MMP-3 and collagen type I or III mRNA levels were observed. Conclusions: Our results reveal that MMP-1, 2 and 9 are significantly down-regulated in a time and pressure dependent fashion following exposure of bladder smooth muscle cells to 20 cm. H2O for as little as 7 hours. TIMP-1 levels increased under similar conditions. These alterations in MMPs and TIMP-1 favor accumulation of extracellular matrix, structural components associated with bladder wall thickness and decreased compliance. These results are consistent with previous data from animal models of complete outlet obstruction. Our results support the concept that pressures 40 cm. H2O or less contribute to molecular changes consistent with decreased compliance associated with bladder dysfunction. 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Link, Google Scholar From the Department of Urology, Riley Hospital for Children, Indiana University, the Department of Biomedical Engineering, Purdue University, Lafayette, Indiana, and the Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byChen L, Wei T, Wang Y, Zhang J, Li H and Wang K (2018) Simulated Bladder Pressure Stimulates Human Bladder Smooth Muscle Cell Proliferation via the PI3K/SGK1 Signaling PathwayJournal of Urology, VOL. 188, NO. 2, (661-667), Online publication date: 1-Aug-2012.Scales C and Wiener J (2018) Evaluating Outcomes of Enterocystoplasty in Patients With Spina Bifida: A Review of the LiteratureJournal of Urology, VOL. 180, NO. 6, (2323-2329), Online publication date: 1-Dec-2008.Lindehall B, Abrahamsson K, Jodal U, Olsson I and Sillén U (2018) Complications of Clean Intermittent Catheterization in Young Females With Myelomeningocele: 10 to 19 Years of FollowupJournal of Urology, VOL. 178, NO. 3, (1053-1055), Online publication date: 1-Sep-2007.Akbal C, Lee S, Packer S, Davis M, Rink R and Kaefer M (2018) Bladder Augmentation With Acellular Dermal Biomatrix in a Diseased Animal ModelJournal of Urology, VOL. 176, NO. 4S, (1706-1711), Online publication date: 1-Oct-2006. Volume 168Issue 6December 2002Page: 2600-2604 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordshydrostatic pressure, matrix metalloproteinases, bladdermuscle, smoothMetricsAuthor Information BJÖRN O. BACKHAUS More articles by this author MARTIN KAEFER Financial interest and/or other relationship with Alza and Pharmacia. More articles by this author KAREN M. HABERSTROH More articles by this author KAREN HILE More articles by this author JIRO NAGATOMI More articles by this author RICHARD C. RINK Financial interest and/or other relationship with Alza, Bayer and Qmed. More articles by this author MARK P. CAIN Financial interest and/or other relationship with Aventis and Pharmacia. More articles by this author ANTHONY CASALE Financial interest and/or other relationship with Aventis-Pasteur, Bayer and Pharmacia. More articles by this author RENA BIZIOS More articles by this author Expand All Advertisement PDF downloadLoading ...