Altered bladder function in transgenic mice expressing rat elastin

Lemack, Gary E.; Szabó, Zoltán; Urban, Zsolt; Boyd, Charles D.; Csiszár, Katalin; Vaughan, E. Darracott; Felsen, Diane

doi:10.1002/(sici)1520-6777(1999)18:1<55::aid-nau8>3.0.co;2-c

Cited by 26 publications

(10 citation statements)

References 28 publications

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“…The viscoelastic properties of the bladder are primarily dependent on the elements contained within the extracellular matrix (4, 64). Elastin, for example, is very compliant compared with collagen (32,45). Elastin contributes mainly to the foot of the passive length-tension curve, while the sharp rising portion reflects the collagen component.…”

Section: Resultsmentioning

confidence: 99%

Bladder smooth muscle organ culture preparation maintains the contractile phenotype

Wang

Kendig

Chang

et al. 2012

American Journal of Physiology-Renal Physiology

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Smooth muscle cells, when subjected to culture, modulate from a contractile to a secretory phenotype. This has hampered the use of cell culture for molecular techniques to study the regulation of smooth muscle biology. The goal of this study was to develop a new organ culture model of bladder smooth muscle (BSM) that would maintain the contractile phenotype and aid in the study of BSM biology. Our results showed that strips of BSM subjected to up to 9 days of organ culture maintained their contractile phenotype, including the ability to achieve near-control levels of force with a temporal profile similar to that of noncultured tissues. The technical aspects of our organ culture preparation that were responsible, in part, for the maintenance of the contractile phenotype were a slight longitudinal stretch during culture and subjection of the strips to daily contraction-relaxation. The tissues contained viable cells throughout the cross section of the strips. There was an increase in extracellular collagenous matrix, resulting in a leftward shift in the passive length-tension relationship. There were no significant changes in the content of smooth muscle-specific α-actin, calponin, h-caldesmon, total myosin heavy chain, protein kinase G, Rho kinase-I, or the ratio of SM1 to SM2 myosin isoforms. Moreover the organ cultured tissues maintained functional voltage-gated calcium channels and large-conductance calcium-activated potassium channels. Therefore, we propose that this novel BSM organ culture model maintains the contractile phenotype and will be a valuable tool for the use in cellular/molecular biology studies of bladder myocytes.

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Section: Resultsmentioning

confidence: 99%

Bladder smooth muscle organ culture preparation maintains the contractile phenotype

Wang

Kendig

Chang

et al. 2012

American Journal of Physiology-Renal Physiology

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“…In animal models, Lemack et al. [7] found increased bladder compliance in transgenic mice overexpressing rat‐elastin compared with their non‐transgenic littermates. Conversely, mice with the same genotype as in this study were found to develop hypertension [19], possibly through the mechanism that the aorta and arteries of elastin‐deficient mice become less distensible (reduced compliance), leading to higher blood pressure during systole.…”

Section: Discussionmentioning

confidence: 99%

“…Elements of the ECM are believed to determine the visco-elastic properties of the bladder [ 14,15 ] . In particular, collagen is thought to provide tensile strength, whereas elastin probably enhances tissue compliance [ 7 ] . In the present study, we found that Eln + / − mice, with approximately one-third less bladder elastin and no signifi cant change in collagen content, had signifi cantly decreased bladder compliance and capacity compared with Wt controls.…”

Section: Discussionmentioning

confidence: 99%

“…To date, most studies addressing bladder function and dysfunction have focused on bladder smooth muscle and its autonomic innervation, whereas the role of ECM, particularly elastic fibres, in normal bladder function and dysfunction remains speculative. Transgenic mice overexpressing rat elastin showed increased bladder compliance compared with their wild‐type littermates [7], indicating that elastin content is positively correlated with bladder compliance. However, there are inconsistent findings of the levels of elastin content in patients with non‐compliant bladders [8,9], highlighting the need for further investigation into the exact role of elastin in bladder function.…”

Section: Introductionmentioning

confidence: 98%

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Altered bladder function in elastin‐deficient mice at baseline and in response to partial bladder outlet obstruction

Jiang

Luttrell

et al. 2011

BJU International

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OBJECTIVE To examine functional and molecular changes of the bladders from elastin-haploinsufficient mice (Eln+/−) at baseline as well as in response to partial bladder outlet obstruction (pBOO). MATERIALS AND METHODS Female Eln+/− and wild type (Wt) mice (3–4 months old) were studied. The bladder elastin content was quantified by measuring desmosine. Mice were divided into two groups to undergo surgery to create pBOO or to undergo sham surgery. Three days after surgery, bladder function was evaluated by in vivo cystometry, and the contractile response of bladder strips exposed to electrical field stimulation (EFS) and carbachol was examined by ex vivo myography. RESULTS The Eln+/−-sham mice had a 33.6% decrease in bladder elastin compared with Wt-sham mice. Cystometry showed significantly decreased bladder compliance and capacity in Eln+/−-sham vs Wt-sham mice; pBOO increased bladder compliance and capacity to a greater extent in Eln+/− mice compared with Wt mice. Bladder strips from Eln+/−-sham mice showed a significantly heightened contractile response to both EFS and carbachol compared with Wt-sham mice. A significantly increased contractile response to carbachol was detected in Wt-pBOO vs Wt-sham but not between Eln+/−-pBOO and Eln+/−-sham mice. CONCLUSION The results that elastin-deficient mice had decreased bladder compliance and capacity and increased bladder contractility; and that Wt-pBOO mice showed an enhanced contractile response to carbachol, but Eln+/−-pBOO mice did not, suggest that elastin is critical for normal bladder function and is involved in bladder response to pBOO.

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“…As is the case in other tissues, deficient or aberrant elastic fiber formation and matrix deposition affects bladder function [368, 369, 373]. Excess levels of CS and dermatan sulfate have been implicated in downregulating elastin secretion by bladder fibroblasts [374, 375].…”

Section: Progress Towards Engineering/regenerating Tissue-type-specifmentioning

confidence: 99%

Advances in biomimetic regeneration of elastic matrix structures

Balakrishnan

Bashur

Ramamurthi

2012

Drug Deliv. and Transl. Res.

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Elastin is a vital component of the extracellular matrix, providing soft connective tissues with the property of elastic recoil following deformation and regulating the cellular response via biomechanical transduction to maintain tissue homeostasis. The limited ability of most adult cells to synthesize elastin precursors and assemble them into mature crosslinked structures has hindered the development of functional tissue-engineered constructs that exhibit the structure and biomechanics of normal native elastic tissues in the body. In diseased tissues, the chronic overexpression of proteolytic enzymes can cause significant matrix degradation, to further limit the accumulation and quality (e.g., fiber formation) of newly deposited elastic matrix. This review provides an overview of the role and importance of elastin and elastic matrix in soft tissues, the challenges to elastic matrix generation in vitro and to regenerative elastic matrix repair in vivo, current biomolecular strategies to enhance elastin deposition and matrix assembly, and the need to concurrently inhibit proteolytic matrix disruption for improving the quantity and quality of elastogenesis. The review further presents biomaterial-based options using scaffolds and nanocarriers for spatio-temporal control over the presentation and release of these biomolecules, to enable biomimetic assembly of clinically relevant native elastic matrix-like superstructures. Finally, this review provides an overview of recent advances and prospects for the application of these strategies to regenerating tissue-type specific elastic matrix structures and superstructures.

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Altered bladder function in transgenic mice expressing rat elastin

Cited by 26 publications

References 28 publications

Bladder smooth muscle organ culture preparation maintains the contractile phenotype

Bladder smooth muscle organ culture preparation maintains the contractile phenotype

Altered bladder function in elastin‐deficient mice at baseline and in response to partial bladder outlet obstruction

Advances in biomimetic regeneration of elastic matrix structures

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