Alterations in the contractile phenotype of the bladder: lessons for understanding physiological and pathological remodelling of smooth muscle

Zderic, Stephen A.; Chacko, Samuel

doi:10.1111/j.1582-4934.2011.01368.x

Cited by 25 publications

(24 citation statements)

References 86 publications

(158 reference statements)

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“…Alterations in bladder smooth muscle contractility underlie various conditions afflicting the lower urinary tract, including overactive bladder secondary to neurologic or inflammatory insults, diabetic cystopathy and lower urinary tract symptoms associated with obstruction [1]. Our findings demonstrating JunB as a major TGFβ1 effector, suggests that JunB-mediated alterations in contractility are likely to contribute to the pathologic bladder contractility that occurs following spinal cord injury, a condition in which TGFβ1 is known to be upregulated [8].…”

Section: Discussionmentioning

confidence: 59%

“…In response to pathologic stimuli, such as mechanical stress, or altered innervation, smooth muscle cells (SMC) undergo phenotypic changes that result in loss of differentiation markers, cellular hypertrophy, increased production of extracellular matrix proteins and eventual loss of contractile function [1]. Although the consequences of such tissue remodeling are evident by the prevalence of diseases associated with aberrant SM function, the molecular mechanisms that regulate SM phenotype in hollow organs other than the vasculature are still incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

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JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility

et al. 2013

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Smooth muscle contraction is a dynamic process driven by acto-myosin interactions that are controlled by multiple regulatory proteins. Our studies have shown that members of the AP-1 transcription factor family control discrete behaviors of smooth muscle cells (SMC) such as growth, migration and fibrosis. However, the role of AP-1 in regulation of smooth muscle contractility is incompletely understood. In this study we show that the AP-1 family member JunB regulates contractility in visceral SMC by altering actin polymerization and myosin light chain phosphorylation. JunB levels are robustly upregulated downstream of transforming growth factor beta-1 (TGFβ1), a known inducer of SMC contractility. RNAi-mediated silencing of JunB in primary human bladder SMC (pBSMC) inhibited cell contractility under both basal and TGFβ1-stimulated conditions, as determined using gel contraction and traction force microscopy assays. JunB knockdown did not alter expression of the contractile proteins α-SMA, calponin or SM22α. However, JunB silencing decreased levels of Rho kinase (ROCK) and myosin light chain (MLC20). Moreover, JunB silencing attenuated phosphorylation of the MLC20 regulatory phosphatase subunit MYPT1 and the actin severing protein cofilin. Consistent with these changes, cells in which JunB was knocked down showed a reduction in the F:G actin ratio in response to TGFβ1. Together these findings demonstrate a novel function for JunB in regulating visceral smooth muscle cell contractility through effects on both myosin and the actin cytoskeleton.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility

et al. 2013

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“…Partial urethral obstruction is relatively common in men with aging, as a result of benign prostate hypertrophy, carcinoma, or calculi, and results in increased back pressure during micturition. During early stages of urethral restriction, which can take years to develop, the bladder undergoes compensatory hypertrophy in order to produce the greater contractile force required to force urine passed the restriction and keep residual urine volumes low (100). These patients present with voiding symptoms, which include urgency, frequency, slowing of the urinary stream, straining to void and nocturia all of which affect quality of life.…”

Section: Urethral Contractile Physiologymentioning

confidence: 99%

Control of Urinary Drainage and Voiding

Hill

2015

Clinical Journal of the American Society of Nephrology

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Urine differs greatly in ion and solute composition from plasma and contains harmful and noxious substances that must be stored for hours and then eliminated when it is socially convenient to do so. The urinary tract that handles this output is composed of a series of pressurizable muscular compartments separated by sphincteric structures. With neural input, these structures coordinate the delivery, collection, and, ultimately, expulsion of urine. Despite large osmotic and chemical gradients in this waste fluid, the bladder maintains a highly impermeable surface in the face of a physically demanding biomechanical environment, which mandates recurring cycles of surface area expansion and increased wall tension during filling, followed by rapid wall compression during voiding. Afferent neuronal inflow from mucosa and submucosa communicates sensory information about bladder fullness, and voiding is initiated consciously through coordinated central and spinal efferent outflow to the detrusor, trigonal internal sphincter, and external urethral sphincter after periods of relative quiescence. Provocative new findings suggest that in some cases, lower urinary tract symptoms, such as incontinence, urgency, frequency, overactivity, and pain may be viewed as a consequence of urothelial defects (either urothelial barrier breakdown or inappropriate signaling from urothelial cells to underlying sensory afferents and potentially interstitial cells). This review describes the physiologic and anatomic mechanisms by which urine is moved from the kidney to the bladder, stored, and then released. Relevant clinical examples of urinary tract dysfunction are also discussed.

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“…An initial development of force enables bladder to implement quick contractile responses, but they also may maintain force for an extended period of time to empty the bladder [1]. Adequate bladder contraction ensures complete urine emptying, while abnormal contractile performance of bladder smooth muscle can contribute to various diseases, such as urinary incontinence, overactive bladder or retention of urine [2,3].…”

Section: Introductionmentioning

confidence: 99%

Carbachol-induced signaling through Thr696-phosphorylation of myosin phosphatase-targeting subunit 1 (MYPT1) in rat bladder smooth muscle cells

et al. 2016

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Purpose Lines of evidence suggest that Rho-associated protein kinase (ROCK) mediated myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation play a central role in smooth muscle contraction. However, the physiological significance of MYPT1 phosphorylation at Thr696 catalyzed by ROCK in bladder smooth muscle remains controversial. We attempt to directly observe the quantitative protein expression of RhoA/ROCK and phosphorylation of MYPT1 at Thr696 after carbachol administration in rat bladder smooth muscle cells (RBMSCs). Materials and Methods Primary cultured smooth muscle cells were obtained from rat bladders. The effects of both concentration and time-course induced by the muscarinic agonist carbachol were investigated by assessing the expression of Rho A/ROCK and MYPT1 phosphorylation at Thr696 using Western blot. Results In the dose-course studies, carbachol showed significant increase of phosphorylation of MYPT1 at Thr696 (p-MYPT1) from concentrations of 15 μM to 100 μM based on Western blot results (p < 0.05, ANOVA test). In the time-course studies, treatment of cells with 15 μM of carbachol significantly enhanced the expression of p-MYPT1 from 3 to 15 hr (p < 0.05, ANOVA test) and induced the expression of Rho A from 10 to 120 min (p < 0.05, ANOVA test). Conclusions Carbachol can induce the expression of ROCK pathway, leading to MYPT1 phosphorylation at Thr696 and thereby sustained RBSMCs contraction.

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Alterations in the contractile phenotype of the bladder: lessons for understanding physiological and pathological remodelling of smooth muscle

Cited by 25 publications

References 86 publications

JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility

JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility

Control of Urinary Drainage and Voiding

Carbachol-induced signaling through Thr696-phosphorylation of myosin phosphatase-targeting subunit 1 (MYPT1) in rat bladder smooth muscle cells

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