scholarly journals Gene expression profiles during tissue remodeling following bladder outlet obstruction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saya Ito ◽  
Takeshi Nomura ◽  
Takashi Ueda ◽  
Shogo Inui ◽  
Yukako Morioka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Expression Patterns ◽  
Outlet Obstruction ◽  
Tissue Remodeling ◽  
Mrna Levels ◽  
Muscular Hypertrophy ◽  
Bladder Smooth Muscle ◽  
Urinary Function

AbstractBladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased bladder smooth muscle proportion and HIF1α mRNA levels compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (DBP), were upregulated only in the mild muscular hypertrophy group. DBP expression levels were increased in bladder smooth muscle cells in response to hypoxic stress. DBP associated with enhancer and promoter regions of NOS3 gene locus and upregulated NOS3 gene expression under hypoxic conditions. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian clock components might be involved in control of urinary function via transcriptional gene regulation in response to hypoxic stimuli.

scholarly journals Gene Expression Profiles During Tissue Remodeling Following Bladder Outlet Obstruction

2021 ◽  
Author(s):  
Saya Ito ◽  
Takeshi Nomura ◽  
Takashi Ueda ◽  
Shogo Inui ◽  
Yukako Morioka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Expression Patterns ◽  
Outlet Obstruction ◽  
Tissue Remodeling ◽  
Mrna Levels ◽  
Hypoxic Stress ◽  
Muscular Hypertrophy ◽  
Urinary Function

Abstract Bladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle and hypoxia-inducible factor 1α (HIF1α) mRNA levels in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased HIF1α mRNA levels and bladder smooth muscle proportion compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (DBP), were upregulated only in the mild muscular hypertrophy group. DBP expression was increased in urinary bladder cells in response to hypoxic stress and induced the upregulation of some genes involved in urinary function. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian rhythms may be involved in urinary function via regulation of gene expression following hypoxic stress.

scholarly journals Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

2017 ◽  
Vol 44 (3) ◽  
pp. 907-919 ◽  
Author(s):  
Qiang Liu ◽  
Deyi Luo ◽  
Tongxin Yang ◽  
Banghua Liao ◽  
Hong Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Structure And Function ◽  
Bladder Function ◽  
Bladder Smooth Muscle ◽  
M3 Receptors ◽  
And Function

Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.

GATA-6 mediates human bladder smooth muscle differentiation: involvement of a novel enhancer element in regulating α-smooth muscle actin gene expression

2007 ◽  
Vol 293 (3) ◽  
pp. C1093-C1102 ◽  
Author(s):  
Akihiro Kanematsu ◽  
Aruna Ramachandran ◽  
Rosalyn M. Adam
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Muscle Differentiation ◽  
Mrna Levels ◽  
Muscle Actin ◽  
Bladder Smooth Muscle ◽  
Human Bladder ◽  
Enhancer Element ◽  
Smooth Muscle Differentiation

Hollow organs exposed to pathological stimuli undergo phenotypic modulation characterized by altered expression of smooth muscle contractile proteins and loss of normal function. The molecular mechanisms that regulate smooth muscle differentiation, especially in organs other than the vasculature, are poorly understood. In this study, we describe a role for the GATA-6 transcription factor in regulation of human bladder smooth muscle differentiation. Knockdown of endogenous GATA-6 in primary human bladder smooth muscle cells (pBSMC) led to decreased mRNA levels of the differentiation markers α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin heavy chain. Similar effects were obtained following downregulation of GATA-6 by forskolin-induced elevation of intracellular cAMP levels. Forskolin treatment of pBSMC abolished recruitment of GATA-6 to the α-SMA promoter in vivo and reduced activity of human α-SMA promoter-directed gene expression by >60%. This inhibitory effect was rescued by enforced expression of wild-type GATA-6 but not by a zinc-finger-deleted mutant, GATA-6-ΔZF, which lacks DNA-binding ability. In silico analysis of a region of the human α-SMA promoter, described previously as a transcriptional enhancer, identified a putative GATA-binding site at position −919/−913. Point mutation of this site in SMA-Luc abrogated GATA-6-induced activation of promoter activity. Together, these results provide the first evidence for a functional role for GATA-6 in regulation of bladder smooth muscle differentiation. In addition, these findings demonstrate that GATA-6 regulates human α-SMA expression via a novel regulatory cis element in the α-SMA promoter-enhancer.

Partial bladder outlet obstruction alters Ca2+ sensitivity of force, but not of MLC phosphorylation, in bladder smooth muscle

2003 ◽  
Vol 285 (4) ◽  
pp. F703-F710 ◽  
Author(s):  
Michaela C. Stanton ◽  
Michele Clement ◽  
Edward J. Macarak ◽  
Stephen A. Zderic ◽  
Robert S. Moreland
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Muscle Cells ◽  
Maximal Velocity ◽  
Bladder Smooth Muscle ◽  
Partial Bladder Outlet Obstruction ◽  
Velocity Of Shortening ◽  
Mlc Phosphorylation

Partial bladder outlet obstruction in the rabbit produces changes in bladder function similar to those seen clinically in patients with obstructive uropathies. Whole organ function is significantly altered, as are the smooth muscle cells inside the bladder wall. This study was designed to determine whether outlet obstruction alters smooth muscle function at the level of contractile filaments. Rabbit bladders were partially obstructed for 2 wk. Triton X-100 was used to provide a detergent-skinned bladder smooth muscle preparation that would allow control of the intracellular environment while the ability to shorten and develop force is maintained. Ca2+-force and Ca2+-myosin light chain (MLC) phosphorylation relations and maximal velocity of shortening were determined. The Ca2+ sensitivity of force was significantly lower in tissues from animals subjected to outlet obstruction compared with tissues from control animals. In contrast, no difference was noted in the Ca2+ sensitivity of MLC phosphorylation. Maximal levels of stress and MLC phosphorylation were similar in both animal groups. Maximal velocity of shortening was significantly slower in tissues from outlet-obstructed animals at all Ca2+ concentrations compared with tissues from control animals. Ultrastructurally, detergent skinning had little effect on structural integrity. Moreover, tissues from obstructed animals showed an increase in the number of sarcolemmal attachment plaque structures. We suggest that partial bladder outlet obstruction produces deleterious (e.g., decrease in Ca2+ sensitivity of force) and compensatory (e.g., increase in membrane attachment plaques) changes in bladder smooth muscle cells.

scholarly journals Calcineurin Mediates Bladder Smooth Muscle Hypertrophy After Bladder Outlet Obstruction

2003 ◽  
Vol 170 (5) ◽  
pp. 2077-2081 ◽  
Author(s):  
KUNIHIRO NOZAKI ◽  
KAZUHITO TOMIZAWA ◽  
TERUHIKO YOKOYAMA ◽  
HIROMI KUMON ◽  
HIDEKI MATSUI
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Muscle Hypertrophy ◽  
Outlet Obstruction ◽  
Bladder Smooth Muscle

Strain Induced Bladder Smooth Muscle Remodeling

2007 ◽  
Author(s):  
Rebecca A. Long ◽  
Aron Parekh ◽  
Michael S. Sacks
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Bladder Wall ◽  
Outlet Obstruction ◽  
Tissue Remodeling ◽  
Bladder Function ◽  
Compensatory Mechanism ◽  
Bladder Smooth Muscle ◽  
Cord Injury

Multiple urinary bladder wall (UBW) pathologies, such as overactive bladder, bladder outlet obstruction, spinal cord injury (SCI) and related neurogenic disorders, and diabetes result in tissue remodeling marked by hypertrophic bladder smooth muscle cells (BSMC) and altered extra-cellular matrix components. This remodeling results in changes in UBW biomechanical properties leading to altered bladder function. Our previous studies have revealed that during the initial areflexic phase of SCI the UBW undergoes profound remodeling that appears to be a compensatory mechanism for the increased wall stretch resulting from over-distension [1, 2]. Remodeling in the bladder wall results in changes in biomechanics and ultimately the ability of the organ to normally fill and void [3]. The stimuli and precise mechanisms that are responsible for bladder remodeling in SCI and the aforementioned pathologies remain unknown. The objective of the present study is to determine the effects of varied in vitro strain on ECM production in the ex vivo rat bladder as a first step toward understanding tissue remodeling in response to strain.

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