| 41. |
- Schroder, A, et al.
(author)
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Regional differences in bladder enlargement and in vitro contractility after outlet obstruction in the rabbit
- 2002
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In: Journal of Urology. - 1527-3792. ; 168:3, s. 1240-1246
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Journal article (peer-reviewed)abstract
- Purpose: Bladder outlet obstruction leads to bladder enlargement and subsequent decreases in contractile function in vivo and in vitro. We determined whether there were regional differences in bladder wall properties and in vitro contractile responses after 2 weeks of bladder outlet obstruction. Materials and Methods: Male rabbits underwent cystometry. The bladder was then filled to 40 ml. and the surface was marked with 2-zero silk knots placed approximately 1 cm. apart. The distance between the knots was measured at 20, 40 and 80 ml. The animals then underwent the creation of surgical obstruction. After 2 weeks the obstruction was removed. Cystometry and measurements were repeated and strips were obtained from defined dorsal and ventral areas. Contractile responses to electrical field stimulation, adenosine triphosphate, carbachol and KCl were determined and compared with strips from unobstructed controls. Results: In vivo expansion during bladder filling occurred evenly throughout the bladder wall in controls and the contractile response to all stimuli was similar in ventral and dorsal strips. After 2 weeks of bladder outlet obstruction the upper dome expanded to a significantly higher degree than the lower bladder body. The response to all stimuli was significantly reduced after bladder outlet obstruction and there was a significantly decreased response to all stimuli in dorsal compared with ventral strips. Strips from the dorsal midline showed a relaxation response to electrical field stimulation at low frequencies, whereas all ventral strips contracted. Conclusions: Functional remodeling after bladder outlet obstruction is a process that does not occur to the same extent throughout the bladder. The obstructed bladder is an inhomogeneous organ with significant regional differences in mechanical and pharmacological properties.
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| 42. |
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| 43. |
- Scott, Rolf Sjuve, et al.
(author)
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The role of desmin in active force transmission and maintenance of structure during growth of urinary bladder.
- 2008
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In: American Journal of Physiology: Cell Physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 295:2, s. 324-331
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Journal article (peer-reviewed)abstract
- The role of the intermediate filament protein desmin in hypertrophy of smooth muscle was examined in desmin deficient mice (Des -/-). A partial obstruction of the urethra was created and after 9-19 days bladder weight increased about 3-fold in both Des -/- and wild type (Des +/+) animals. Bladder growth was associated with synthesis of actin and myosin. In the hypertrophic Des +/+ bladder the relative content of desmin increased. In Des -/- mice desmin was absent. No alterations in the amount of vimentin were observed. Although Des -/- obstructed bladders were capable of growth they had structural changes with partial disruption of the wall. Des-/- bladders had slightly lower passive stress and significantly lower active stress compared to Des+/+. Des-/- preparations had lower shortening velocity. During hypertrophy these structural and mechanical alterations in the Des-/- urinary bladder became more pronounced. In conclusion, desmin in the bladder smooth muscle is not needed for growth but has a role in active force transmission and maintenance of wall structure. Key words: smooth muscle, intermediate filaments, desmin, transgenic.
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| 44. |
- Semerdzhiev, Y, et al.
(author)
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Cystometric and in vitro muscle studies of cystoplastic appendiceal segments in the rat
- 2006
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In: Neurourology and Urodynamics. - : John Wiley and Sons, Ltd. - 0733-2467 .- 1520-6777. ; 25:3, s. 259-267
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Journal article (peer-reviewed)abstract
- AIMS: The functional integration of the smooth muscle of enterocystoplasties into the detrusor muscle was investigated in an awake-rat cystometry model and in vitro.METHODS: The upper fourth of the bladder was removed, and a detubularized appendiceal segment (7 x 7 mm), with preserved vasculature, was incorporated into the bladder. After 1 or 3 months, a catheter was fixed to the top of the bladders. After a 3-day recovery, cystometries were performed. In separate experiments, agonist and nerve-induced responses were evaluated on isolated bladder strips.RESULTS: Cystometries revealed reduced basal pressure and micturition pressure in enterocystoplasty (ECP) bladders. Bladder capacity and micturition volume were increased. Threshold pressure (pressure immediately before micturition) was significantly lower at 1 month, but not at 3 months. Bladder compliance was significantly higher in the operated at 1 month but not at 3 months. Threshold tension did not differ between control and corresponding operated groups. Residual urine was significantly higher in the operated groups. ECP strips showed increased maximal contractions to nerve stimulation, to levels similar to those of detrusor strips. Maximal responses to carbachol increased to levels between those of intestine and detrusor. The inhibitory effect of scopolamine on nerve induced contractions increased to levels similar to those for detrusor. Purinergic activation had no effect on intestinal or ECP strips, but contracted detrusor muscle.CONCLUSIONS: The smooth muscle of the bowel segment in rat ECP bladders underwent a partial change in the response to nerve stimulation from that of intestine towards that of detrusor. The cystometry experiments suggested a partial functional integration of the ECP segment into the detrusor.
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| 45. |
- Shakirova, Yulia, et al.
(author)
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Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.
- 2010
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In: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 649, s. 362-368
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Journal article (peer-reviewed)abstract
- Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6weeks caused a 2.56-fold increase in the number of smooth muscle caveolae per μm membrane. No changes in the expression of caveolin-1 or cavin-1, normalized to β-actin were seen, but membrane area per unit muscle volume dropped to 0.346. Hypertrophy was associated with altered contraction in response to carbachol. The effect on contraction of cholesterol desorption, which disrupts lipid rafts and caveolae, was however not changed. Contraction in response to bradykinin resisted mβcd in control destrusor, but was inhibited by it after 6weeks of obstruction. It is concluded that rat detrusor hypertrophy leads to an increased number of caveolae per unit membrane area. This change is due to a reduction of membrane area per volume muscle and it does not play a role for cholinergic activation, but promotes contraction in response to bradykinin after long-term obstruction.
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| 46. |
- Shakirova, Yulia, et al.
(author)
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Human urinary bladder smooth muscle is dependent on membrane cholesterol for cholinergic activation.
- 2010
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In: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 634, s. 142-148
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Journal article (peer-reviewed)abstract
- Voiding is mediated by muscarinic receptors in urinary bladder smooth muscle cells. Lipid rafts and caveolae are cholesterol enriched membrane domains that modulate the activity of G protein-coupled receptors and second messenger systems. Conflicting findings regarding sensitivity of muscarinic signalling to cholesterol desorption, which perturbs lipid rafts and caveolae, have been reported, and no study has used human urinary bladder. Here, the dependence of human bladder muscarinic receptor signalling on plasma membrane cholesterol was examined. Nerve-mediated contraction, elicited by electrical field stimulation of human bladder strips, was impaired by desorption of cholesterol using methyl-beta-cyclodextrin, and the concentration-response curve for the muscarinic agonist carbachol was right-shifted. No effect of cholesterol desorption was observed in rat, and in mouse increased maximum contraction was seen. Expression of caveolin-1, PLC(beta1) and M(3) muscarinic receptors did not differ between species in a manner that would explain the differential sensitivity to cholesterol desorption. In human bladder, threshold depolarisation eliminated the difference between cyclodextrin-treated and control preparations. Contraction elicited by depolarisation per se was not affected. M(3) muscarinic receptors appeared clustered along plasma membrane profiles as shown by immunohistochemical staining of human bladder, but no redistribution in association with cholesterol reduction were seen. Thus, muscarinic receptor-induced contraction of the urinary bladder exhibits species-specific differences in its sensitivity to cholesterol desorption suggesting differential roles of lipid rafts/caveolae in muscarinic receptor signalling between species.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Swärd, Karl, et al.
(author)
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Identification of the intermediate filament protein synemin/SYNM as a target of myocardin family coactivators
- 2019
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In: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 317:6, s. 1128-1142
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Journal article (peer-reviewed)abstract
- Myocardin (MYOCD) is a critical regulator of smooth muscle cell (SMC) differentiation, but its transcriptional targets remain to be exhaustively characterized, especially at the protein level. Here we leveraged human RNA and protein expression data to identify novel potential MYOCD targets. Using correlation analyses we found several targets that we could confirm at the protein level, including SORBS1, SLMAP, SYNM, and MCAM. We focused on SYNM, which encodes the intermediate filament protein synemin. SYNM rivalled smooth muscle myosin (MYH11) for SMC specificity and was controlled at the mRNA and protein levels by all myocardin-related transcription factors (MRTFs: MYOCD, MRTF-A/MKL1, and MRTF-B/MKL2). MRTF activity is regulated by the ratio of filamentous to globular actin, and SYNM was accordingly reduced by interventions that depolymerize actin, such as latrunculin treatment and overexpression of constitutively active cofilin. Many MRTF target genes depend on serum response factor (SRF), but SYNM lacked SRF-binding motifs in its proximal promoter, which was not directly regulated by MYOCD. Furthermore, SYNM resisted SRF silencing, yet the time course of induction closely paralleled that of the SRF-dependent target gene ACTA2. SYNM was repressed by the ternary complex factor (TCF) FLI1 and was increased in mouse embryonic fibroblasts lacking three classical TCFs (ELK1, ELK3, and ELK4). Imaging showed colocalization of SYNM with the intermediate filament proteins desmin and vimentin, and MRTF-A/MKL1 increased SYNM-containing intermediate filaments in SMCs. These studies identify SYNM as a novel SRF-independent target of myocardin that is abundantly expressed in all SMCs.
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