scholarly journals The Role of LIM Kinase in the Male Urogenital System

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 78
Author(s):  
Juhyun Park ◽  
Soo Woong Kim ◽  
Min Chul Cho

The LIM kinases (LIMK1 and LIMK2), known as downstream effectors, and the Rho-associated protein kinase (ROCK), a regulator of actin dynamics, have effects on a diverse set of cellular functions. The LIM kinases are involved in the function of the male urogenital system by smooth muscle contraction via phosphorylation of cofilin and subsequent actin cytoskeleton reorganization. Although LIMK1 and LIMK2 share sequence similarities as serine protein kinases, different tissue distribution patterns and distinct localization during cell cycle progression suggest other biological functions for each kinase. During meiosis and mitosis, the LIMK1/2–cofilin signaling facilitates the orchestrated chromatin remodeling between gametogenesis and the actin cytoskeleton. A splicing variant of the LIMK2 transcript was expressed only in the testis. Moreover, positive signals with LIMK2-specific antibodies were detected mainly in the nucleus of the differentiated stages of germ cells, such as spermatocytes and early round spermatids. LIMK2 plays a vital role in proper spermatogenesis, such as meiotic processes of spermatogenesis after puberty. On the other hand, the literature evidence revealed that a reduction in LIMK1 expression enhanced the inhibitory effects of a ROCK inhibitor on the smooth muscle contraction of the human prostate. LIMK1 may have a role in urethral obstruction and bladder outlet obstruction in men with benign prostatic hyperplasia. Moreover, LIMK1 expression was reduced in urethral stricture. The reduced LIMK1 expression caused the impaired proliferation and migration of urethral fibroblasts. In addition, the activated LIMK2–cofilin pathway contributes to cavernosal fibrosis after cavernosal nerve injury. Recent evidence demonstrated that short-term inhibition of LIMK2 from the immediate post-injury period prevented cavernosal fibrosis and improved erectile function in a rat model of cavernosal nerve injury. Furthermore, chronic inhibition of the LIMK2–cofilin pathway significantly restrained the cavernosal veno-occlusive dysfunction, the primary pathophysiologic mechanism of post-prostatectomy erectile dysfunction through suppressing fibrosis in the corpus cavernosum. In conclusion, the LIM kinases–cofilin pathway appears to play a role in the function of the male urogenital system through actin cytoskeleton reorganization and contributes to the pathogenesis of several urogenital diseases. Therefore, LIM kinases may be a potential treatment target in urogenital disorder.

2018 ◽  
Vol 175 (11) ◽  
pp. 2077-2096 ◽  
Author(s):  
Qingfeng Yu ◽  
Christian Gratzke ◽  
Yiming Wang ◽  
Annika Herlemann ◽  
Christian Maximilian Sterr ◽  
...  

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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