scholarly journals Inhibition of prostate smooth muscle contraction and prostate stromal cell growth by the inhibitors of Rac, NSC23766 and EHT1864

2015 ◽  
Vol 172 (11) ◽  
pp. 2905-2917 ◽  
Author(s):  
Y Wang ◽  
T Kunit ◽  
A Ciotkowska ◽  
B Rutz ◽  
A Schreiber ◽  
...  
The Prostate ◽  
2021 ◽  
Author(s):  
Alexander Tamalunas ◽  
Cora Sauckel ◽  
Anna Ciotkowska ◽  
Beata Rutz ◽  
Ruixiao Wang ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153312 ◽  
Author(s):  
Yiming Wang ◽  
Christian Gratzke ◽  
Alexander Tamalunas ◽  
Nicolas Wiemer ◽  
Anna Ciotkowska ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaolong Wang ◽  
Yiming Wang ◽  
Christian Gratzke ◽  
Christian Sterr ◽  
Qingfeng Yu ◽  
...  

Epidemiologic studies revealed a context between lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and metabolic syndrome. However, molecular mechanisms underlying this relationship are largely unknown. Prostate enlargement and increased prostate smooth muscle tone are important factors in the pathophysiology of LUTS suggestive of BPH. In the present study, we studied effects of the metabolic hormone ghrelin on prostate enlargement in rats with experimentally induced BPH, growth of cultured stromal cells from human prostate (WPMY-1), and smooth muscle contraction of human prostate tissues. Ghrelin (20 nmol/kg daily, p.o., 2 weeks) increased prostate size in rats with testosterone-induced BPH. Microarray identified 114 ghrelin-upregulated genes (2-fold or more) in these prostates, with possible roles in growth, smooth muscle contraction, or metabolism. 12 genes were selected for further analyses. In human prostate tissues, mRNA levels of 11 of them correlated positively with ghrelin receptor (GHSR) expression, but only two with the degree of BPH. Accordingly, no correlation was evident between GHSR expression level and BPH in human prostate tissues. In WPMY-1 cells, the GHRS agonist MK0677 upregulated 11 of the selected genes. MK0677 induced proliferation of WPMY-1 cells, shown by EdU assay, colony formation, proliferation markers, flow cytometry, and viability. In myographic measurements, GHSR agonists enhanced contractions of human prostate strips. Together, ghrelin may aggravate prostate enlargement, stromal cell growth, and prostate smooth muscle contraction in BPH. Ghrelin may deteriorate urethral obstruction independently from BPH, qualifying the ghrelin system as an attractive new target to be tested for LUTS treatment in BPH.


2021 ◽  
Vol 82 (5) ◽  
Author(s):  
Hannah J. Pybus ◽  
Amanda L. Tatler ◽  
Lowell T. Edgar ◽  
Reuben D. O’Dea ◽  
Bindi S. Brook

AbstractPrecision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely used ex vivo assay to investigate bronchoconstriction and, more recently, mechanical activation of pro-remodelling cytokines in asthmatic airways. We develop a nonlinear fibre-reinforced biomechanical model accounting for smooth muscle contraction and extracellular matrix strain-stiffening. Through numerical simulation, we describe the stresses and contractile responses of an airway within a PCLS of finite thickness, exposing the importance of smooth muscle contraction on the local stress state within the airway. We then consider two simplifying limits of the model (a membrane representation and an asymptotic reduction in the thin-PCLS-limit), that permit analytical progress. Comparison against numerical solution of the full problem shows that the asymptotic reduction successfully captures the key elements of the full model behaviour. The more tractable reduced model that we develop is suitable to be employed in investigations to elucidate the time-dependent feedback mechanisms linking airway mechanics and cytokine activation in asthma.


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