The Experts below are selected from a list of 107997 Experts worldwide ranked by ideXlab platform
Dale D Tang - One of the best experts on this subject based on the ideXlab platform.
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role and regulation of abelson tyrosine kinase in crk associated substrate profilin 1 interaction and airway smooth Muscle Contraction
Respiratory Research, 2018Co-Authors: Yinna Wang, Ruping Wang, Alyssa C Rezey, Dale D TangAbstract:Airway smooth Muscle Contraction is critical for maintenance of appropriate airway tone, and has been implicated in asthma pathogenesis. Smooth Muscle Contraction requires an “engine” (myosin activation) and a “transmission system” (actin cytoskeletal remodeling). However, the mechanisms that control actin remodeling in smooth Muscle are not fully elucidated. The adapter protein Crk-associated substrate (CAS) regulates actin dynamics and the Contraction in smooth Muscle. In addition, profilin-1 (Pfn-1) and Abelson tyrosine kinase (c-Abl) are also involved in smooth Muscle Contraction. The interplays among CAS, Pfn-1 and c-Abl in smooth Muscle have not been previously investigated. The association of CAS with Pfn-1 in mouse tracheal rings was evaluated by co-immunoprecipitation. Tracheal rings from c-Abl conditional knockout mice were used to assess the roles of c-Abl in the protein-protein interaction and smooth Muscle Contraction. Decoy peptides were utilized to evaluate the importance of CAS/Pfn-1 coupling in smooth Muscle Contraction. Stimulation with acetylcholine (ACh) increased the interaction of CAS with Pfn-1 in smooth Muscle, which was regulated by CAS tyrosine phosphorylation and c-Abl. The CAS/Pfn-1 coupling was also modified by the phosphorylation of cortactin (a protein implicated in Pfn-1 activation). In addition, ACh activation promoted the spatial redistribution of CAS and Pfn-1 in smooth Muscle cells, which was reduced by c-Abl knockdown. Inhibition of CAS/Pfn-1 interaction by a decoy peptide attenuated the ACh-induced actin polymerization and Contraction without affecting myosin light chain phosphorylation. Furthermore, treatment with the Src inhibitor PP2 and the actin polymerization inhibitor latrunculin A attenuated the ACh-induced c-Abl tyrosine phosphorylation (an indication of c-Abl activation). Our results suggest a novel activation loop in airway smooth Muscle: c-Abl promotes the CAS/Pfn-1 coupling and actin polymerization, which conversely facilitates c-Abl activation. The positive feedback may render c-Abl in active state after contractile stimulation.
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Role and regulation of Abelson tyrosine kinase in Crk-associated substrate/profilin-1 interaction and airway smooth Muscle Contraction
Respiratory Research, 2018Co-Authors: Yinna Wang, Ruping Wang, Alyssa C Rezey, Dale D TangAbstract:Background Airway smooth Muscle Contraction is critical for maintenance of appropriate airway tone, and has been implicated in asthma pathogenesis. Smooth Muscle Contraction requires an “engine” (myosin activation) and a “transmission system” (actin cytoskeletal remodeling). However, the mechanisms that control actin remodeling in smooth Muscle are not fully elucidated. The adapter protein Crk-associated substrate (CAS) regulates actin dynamics and the Contraction in smooth Muscle. In addition, profilin-1 (Pfn-1) and Abelson tyrosine kinase (c-Abl) are also involved in smooth Muscle Contraction. The interplays among CAS, Pfn-1 and c-Abl in smooth Muscle have not been previously investigated. Methods The association of CAS with Pfn-1 in mouse tracheal rings was evaluated by co-immunoprecipitation. Tracheal rings from c-Abl conditional knockout mice were used to assess the roles of c-Abl in the protein-protein interaction and smooth Muscle Contraction. Decoy peptides were utilized to evaluate the importance of CAS/Pfn-1 coupling in smooth Muscle Contraction. Results Stimulation with acetylcholine (ACh) increased the interaction of CAS with Pfn-1 in smooth Muscle, which was regulated by CAS tyrosine phosphorylation and c-Abl. The CAS/Pfn-1 coupling was also modified by the phosphorylation of cortactin (a protein implicated in Pfn-1 activation). In addition, ACh activation promoted the spatial redistribution of CAS and Pfn-1 in smooth Muscle cells, which was reduced by c-Abl knockdown. Inhibition of CAS/Pfn-1 interaction by a decoy peptide attenuated the ACh-induced actin polymerization and Contraction without affecting myosin light chain phosphorylation. Furthermore, treatment with the Src inhibitor PP2 and the actin polymerization inhibitor latrunculin A attenuated the ACh-induced c-Abl tyrosine phosphorylation (an indication of c-Abl activation). Conclusions Our results suggest a novel activation loop in airway smooth Muscle: c-Abl promotes the CAS/Pfn-1 coupling and actin polymerization, which conversely facilitates c-Abl activation. The positive feedback may render c-Abl in active state after contractile stimulation.
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critical role of actin associated proteins in smooth Muscle Contraction cell proliferation airway hyperresponsiveness and airway remodeling
Respiratory Research, 2015Co-Authors: Dale D TangAbstract:Asthma is characterized by airway hyperresponsiveness and airway remodeling, which are largely attributed to increased airway smooth Muscle contractility and cell proliferation. It is known that both chemical and mechanical stimulation regulates smooth Muscle Contraction. Recent studies suggest that contractile activation and mechanical stretch induce actin cytoskeletal remodeling in smooth Muscle. However, the mechanisms that control actin cytoskeletal reorganization are not completely elucidated. This review summarizes our current understanding regarding how actin-associated proteins may regulate remodeling of the actin cytoskeleton in airway smooth Muscle. In particular, there is accumulating evidence to suggest that Abelson tyrosine kinase (Abl) plays a critical role in regulating airway smooth Muscle Contraction and cell proliferation in vitro, and airway hyperresponsiveness and remodeling in vivo. These studies indicate that Abl may be a novel target for the development of new therapy to treat asthma.
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the association of cortactin with profilin 1 is critical for smooth Muscle Contraction
Journal of Biological Chemistry, 2014Co-Authors: Ruping Wang, Rachel A Cleary, Jia Li, Dale D TangAbstract:Profilin-1 (Pfn-1) is an actin-regulatory protein that has a role in modulating smooth Muscle Contraction. However, the mechanisms that regulate Pfn-1 in smooth Muscle are not fully understood. Here, stimulation with acetylcholine induced an increase in the association of the adapter protein cortactin with Pfn-1 in smooth Muscle cells/tissues. Furthermore, disruption of the protein/protein interaction by a cell-permeable peptide (CTTN-I peptide) attenuated actin polymerization and smooth Muscle Contraction without affecting myosin light chain phosphorylation at Ser-19. Knockdown of cortactin by lentivirus-mediated RNAi also diminished actin polymerization and smooth Muscle force development. However, cortactin knockdown did not affect myosin activation. In addition, cortactin phosphorylation has been implicated in nonMuscle cell migration. In this study, acetylcholine stimulation induced cortactin phosphorylation at Tyr-421 in smooth Muscle cells. Phenylalanine substitution at this position impaired cortactin/Pfn-1 interaction in response to contractile activation. c-Abl is a tyrosine kinase that is necessary for actin dynamics and Contraction in smooth Muscle. Here, c-Abl silencing inhibited the agonist-induced cortactin phosphorylation and the association of cortactin with Pfn-1. Finally, treatment with CTTN-I peptide reduced airway resistance and smooth Muscle hyperreactivity in a murine model of asthma. These results suggest that the interaction of cortactin with Pfn-1 plays a pivotal role in regulating actin dynamics, smooth Muscle Contraction, and airway hyperresponsiveness in asthma. The association of cortactin with Pfn-1 is regulated by c-Abl-mediated cortactin phosphorylation.
Constantinos N Maganaris - One of the best experts on this subject based on the ideXlab platform.
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in vivo changes in the human patellar tendon moment arm length with different modes and intensities of Muscle Contraction
Journal of Biomechanics, 2007Co-Authors: Dimitrios Tsaopoulos, Vasilios Baltzopoulos, Paula J Richards, Constantinos N MaganarisAbstract:Abstract The purpose of this study was to examine the effect of different Muscle Contraction modes and intensities on patellar tendon moment arm length ( d PT ) . Five men performed isokinetic concentric, eccentric and passive knee extensions at an angular velocity of 60 deg/s and six men performed gradually increasing to maximum effort isometric Muscle Contractions at 90 ∘ and 20 ∘ of knee flexion. During the tests, lateral X-ray fluoroscopy imaging was used to scan the knee joint. The d PT differences between the passive state and the isokinetic concentric and extension were quantified at 15 ∘ intervals of knee joint flexion angle. Furthermore, the changes of the d PT as a function of the isometric Muscle Contraction intensities were determined during the isometric knee extension at 90 ∘ and 20 ∘ of knee joint flexion. Muscle Contraction-induced changes in knee joint flexion angle during the isometric Muscle Contraction were also taken into account for the d PT measurements. During the two isometric knee extensions, d PT increased from rest to maximum voluntary Muscle Contraction (MVC) by 14–15%. However, when changes in knee joint flexion angle induced by the Muscle Contraction were taken into account, d PT during MVC increased by 6–26% compared with rest. Moreover, d PT increased during concentric and eccentric knee extension by 3–15%, depending on knee flexion angle, compared with passive knee extension. These findings have important implications for estimating musculoskeletal loads using modelling under static and dynamic conditions.
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in vivo changes in the human patellar tendon moment arm length with different modes and intensities of Muscle Contraction
Journal of Biomechanics, 2007Co-Authors: Dimitrios Tsaopoulos, Vasilios Baltzopoulos, Paula J Richards, Constantinos N MaganarisAbstract:The purpose of this study was to examine the effect of different Muscle Contraction modes and intensities on patellar tendon moment arm length (d(PT)). Five men performed isokinetic concentric, eccentric and passive knee extensions at an angular velocity of 60 deg/s and six men performed gradually increasing to maximum effort isometric Muscle Contractions at 90( composite function) and 20( composite function) of knee flexion. During the tests, lateral X-ray fluoroscopy imaging was used to scan the knee joint. The d(PT) differences between the passive state and the isokinetic concentric and extension were quantified at 15( composite function) intervals of knee joint flexion angle. Furthermore, the changes of the d(PT) as a function of the isometric Muscle Contraction intensities were determined during the isometric knee extension at 90( composite function) and 20( composite function) of knee joint flexion. Muscle Contraction-induced changes in knee joint flexion angle during the isometric Muscle Contraction were also taken into account for the d(PT) measurements. During the two isometric knee extensions, d(PT) increased from rest to maximum voluntary Muscle Contraction (MVC) by 14-15%. However, when changes in knee joint flexion angle induced by the Muscle Contraction were taken into account, d(PT) during MVC increased by 6-26% compared with rest. Moreover, d(PT) increased during concentric and eccentric knee extension by 3-15%, depending on knee flexion angle, compared with passive knee extension. These findings have important implications for estimating musculoskeletal loads using modelling under static and dynamic conditions.
Christian G Stief - One of the best experts on this subject based on the ideXlab platform.
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MP06-10 INHIBITION OF PROSTATE SMOOTH Muscle Contraction BY NAV2729 SUGGESTS PROMOTION OF PROSTATE SMOOTH Muscle Contraction BY ADP RIBOSYLATION FACTOR 6
The Journal of Urology, 2019Co-Authors: Qingfeng Yu, Christian Gratzke, Paul Kuppermann, Annika Herlemann, Alexander Tamalunas, Beata Rutz, Anna Ciotkowska, Raphaela Waidelich, Yiming Wang, Christian G StiefAbstract:INTRODUCTION AND OBJECTIVES:In benign prostatic hyperplasia, prostate smooth Muscle Contraction drives urethral obstruction, resulting in lower urinary tract symptoms. Inhibition of prostate contra...
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Inhibition of Prostate Smooth Muscle Contraction by Inhibitors of Polo-Like Kinases
Frontiers in Physiology, 2018Co-Authors: Martin Hennenberg, Qingfeng Yu, Paul Kuppermann, Annika Herlemann, Alexander Tamalunas, Beata Rutz, Anna Ciotkowska, Frank Strittmatter, Yiming Wang, Christian G StiefAbstract:Background: Prostate smooth Muscle Contraction plays an important role for pathophysiology and treatment of male lower urinary tract symptoms (LUTS) but is incompletely understood. Because the efficacy of available medication is limited, novel options and improved understanding of prostate smooth Muscle Contraction are mandatory. Recently, a possible role of polo-like kinase 1 (PLK1) has been suggested for smooth Muscle Contraction outside the lower urinary tract. Here, we examined effects of PLK inhibitors on Contraction of human prostate tissue. Methods: Prostate tissues were obtained from radical prostatectomy. RT-PCR, Western blot and immunofluorescence were performed to detect PLK expression and phosphorylated PLK. Smooth Muscle Contractions were induced by electric field stimulation (EFS), α1-agonists, endothelin-1, or the thromboxane A2 analogue U46619 in organ bath. Results: RT-PCR, Western blot, and immunofluorescence suggested expression of PLK1 in the human prostate, which may be located and active in smooth Muscle cells. EFS-induced Contractions of prostate strips were reduced by SBE 13 (1 µM), cyclapolin 9 (3 µM), TAK 960 (100 nM), and Ro 3280 (100 nM). SBE 13 and cyclapolin 9 inhibited Contractions by the α1-agonists methoxamine, phenylephrine, and noradrenaline. In contrast, no effects of SBE 13 or cyclapolin 9 on endothelin-1- or U46619-induced Contractions were observed. Conclusions: Alpha1-adrenergic smooth Muscle Contraction in the human prostate can be inhibited by PLK inhibitors. PLK-dependent signaling may be a new pathway, which promotes α1-adrenergic Contraction of prostate smooth Muscle cells. As Contractions by endothelin and U46619 are not susceptible to PLK inhibition, this reflects divergent regulation of adrenergic and non-adrenergic prostate smooth Muscle Contraction.
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Inhibition of human prostate smooth Muscle Contraction by the LIM kinase inhibitors, SR7826 and LIMKi3.
British Journal of Pharmacology, 2018Co-Authors: Qingfeng Yu, Christian Gratzke, Annika Herlemann, Beata Rutz, Anna Ciotkowska, Christian Sterr, Frank Strittmatter, Yiming Wang, Xiaolong Wang, Christian G StiefAbstract:LUTS refer to a group of urological symptoms that are caused by multifactorial aetiology. The prevalence of LUTS increases with age, and will thereby lead to heavy economic burden for the society. In men with benign prostate hyperplasia, increased smooth Muscle tone in the prostate could result in bladder outlet obstruction and subsequent symptoms of lower urinary tract. Pharmacological treatment aiming to inhibit prostate smooth Muscle Contraction is considered as the option of first choice. However, the efficacy of current available treatment options is limited, thereby, improved understanding in the mechanisms of prostate smooth Muscle Contraction and development of novel targets for medical therapy are warranted. Previous studies have reported that LIMK (LIMK1 and LIMK2) phosphorylate cofilin and act as regulators of actin-myosin cytoskeletal dynamics, which result in actin polymerization, filament assemble, and stress fiber formation in smooth Muscle cells. This may suggest that LIMKs promote smooth Muscle Contraction, however, not any associated study has been conducted. In this project, we aimed to explore the effects of LIMK inhibitors on prostate smooth Muscle Contraction. Human prostate tissues were obtained from patients who underwent radical prostatectomy. RT-PCR, western blot and immunofluorescence were performed to detect LIMK in smooth Muscle cells of prostate tissues. Phosphorylation of cofilin, a LIMK substrate, was detected by a phospho-specific antibody. Effects of LIMK inhibitors on smooth Muscle Contraction of prostate strips were performed with organ bath. Expression of LIMK in smooth Muscle cells of prostate tissues was suggested by RT-PCR, Western blot and immunofluorescence, while higher expression level of LIMK was detected in prostate tissues than that in WPMY-1 cells. Two LIMK inhibitors, SR7826 (1 µM) and LIMKi3 (1 µM), showed significant effects on inhibiting Contractions of prostate strips, which were induced by the α1-adrenoceptor agonists, noradrenaline, phenylephrine and methoxamine, by the thromboxane A2 analogue, U46619, and by EFS. Reduced phosphorylation of cofilin in prostate tissues treated with inhibitors was observed, which confirmed LIMK inhibition by SR7826 and LIMKi3. In WPMY-1 cells, a line of cultured cells from the prostate stroma, SR7826 and LIMKi3 were observed to cause breakdown of actin filaments and reduced viability in a concentration-dependent manner. Together, this is the first study to explore the effects of small molecule LIMK inhibitors on regulating prostate smooth Muscle Contraction. The present study suggested that LIMKs promote prostate smooth Muscle Contraction by phosphorylating cofilin and subsequent causing actin organization, which could be inhibited by small molecule LIMK inhibitors, SR7826 and LIMKi3. Therefore, this project provides a possible novel therapy target for LUTS, although in vivo studies using animal models would be still warranted before clinical application.
Dimitrios Tsaopoulos - One of the best experts on this subject based on the ideXlab platform.
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in vivo changes in the human patellar tendon moment arm length with different modes and intensities of Muscle Contraction
Journal of Biomechanics, 2007Co-Authors: Dimitrios Tsaopoulos, Vasilios Baltzopoulos, Paula J Richards, Constantinos N MaganarisAbstract:Abstract The purpose of this study was to examine the effect of different Muscle Contraction modes and intensities on patellar tendon moment arm length ( d PT ) . Five men performed isokinetic concentric, eccentric and passive knee extensions at an angular velocity of 60 deg/s and six men performed gradually increasing to maximum effort isometric Muscle Contractions at 90 ∘ and 20 ∘ of knee flexion. During the tests, lateral X-ray fluoroscopy imaging was used to scan the knee joint. The d PT differences between the passive state and the isokinetic concentric and extension were quantified at 15 ∘ intervals of knee joint flexion angle. Furthermore, the changes of the d PT as a function of the isometric Muscle Contraction intensities were determined during the isometric knee extension at 90 ∘ and 20 ∘ of knee joint flexion. Muscle Contraction-induced changes in knee joint flexion angle during the isometric Muscle Contraction were also taken into account for the d PT measurements. During the two isometric knee extensions, d PT increased from rest to maximum voluntary Muscle Contraction (MVC) by 14–15%. However, when changes in knee joint flexion angle induced by the Muscle Contraction were taken into account, d PT during MVC increased by 6–26% compared with rest. Moreover, d PT increased during concentric and eccentric knee extension by 3–15%, depending on knee flexion angle, compared with passive knee extension. These findings have important implications for estimating musculoskeletal loads using modelling under static and dynamic conditions.
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in vivo changes in the human patellar tendon moment arm length with different modes and intensities of Muscle Contraction
Journal of Biomechanics, 2007Co-Authors: Dimitrios Tsaopoulos, Vasilios Baltzopoulos, Paula J Richards, Constantinos N MaganarisAbstract:The purpose of this study was to examine the effect of different Muscle Contraction modes and intensities on patellar tendon moment arm length (d(PT)). Five men performed isokinetic concentric, eccentric and passive knee extensions at an angular velocity of 60 deg/s and six men performed gradually increasing to maximum effort isometric Muscle Contractions at 90( composite function) and 20( composite function) of knee flexion. During the tests, lateral X-ray fluoroscopy imaging was used to scan the knee joint. The d(PT) differences between the passive state and the isokinetic concentric and extension were quantified at 15( composite function) intervals of knee joint flexion angle. Furthermore, the changes of the d(PT) as a function of the isometric Muscle Contraction intensities were determined during the isometric knee extension at 90( composite function) and 20( composite function) of knee joint flexion. Muscle Contraction-induced changes in knee joint flexion angle during the isometric Muscle Contraction were also taken into account for the d(PT) measurements. During the two isometric knee extensions, d(PT) increased from rest to maximum voluntary Muscle Contraction (MVC) by 14-15%. However, when changes in knee joint flexion angle induced by the Muscle Contraction were taken into account, d(PT) during MVC increased by 6-26% compared with rest. Moreover, d(PT) increased during concentric and eccentric knee extension by 3-15%, depending on knee flexion angle, compared with passive knee extension. These findings have important implications for estimating musculoskeletal loads using modelling under static and dynamic conditions.
Qingfeng Yu - One of the best experts on this subject based on the ideXlab platform.
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MP06-10 INHIBITION OF PROSTATE SMOOTH Muscle Contraction BY NAV2729 SUGGESTS PROMOTION OF PROSTATE SMOOTH Muscle Contraction BY ADP RIBOSYLATION FACTOR 6
The Journal of Urology, 2019Co-Authors: Qingfeng Yu, Christian Gratzke, Paul Kuppermann, Annika Herlemann, Alexander Tamalunas, Beata Rutz, Anna Ciotkowska, Raphaela Waidelich, Yiming Wang, Christian G StiefAbstract:INTRODUCTION AND OBJECTIVES:In benign prostatic hyperplasia, prostate smooth Muscle Contraction drives urethral obstruction, resulting in lower urinary tract symptoms. Inhibition of prostate contra...
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Inhibition of Prostate Smooth Muscle Contraction by Inhibitors of Polo-Like Kinases
Frontiers in Physiology, 2018Co-Authors: Martin Hennenberg, Qingfeng Yu, Paul Kuppermann, Annika Herlemann, Alexander Tamalunas, Beata Rutz, Anna Ciotkowska, Frank Strittmatter, Yiming Wang, Christian G StiefAbstract:Background: Prostate smooth Muscle Contraction plays an important role for pathophysiology and treatment of male lower urinary tract symptoms (LUTS) but is incompletely understood. Because the efficacy of available medication is limited, novel options and improved understanding of prostate smooth Muscle Contraction are mandatory. Recently, a possible role of polo-like kinase 1 (PLK1) has been suggested for smooth Muscle Contraction outside the lower urinary tract. Here, we examined effects of PLK inhibitors on Contraction of human prostate tissue. Methods: Prostate tissues were obtained from radical prostatectomy. RT-PCR, Western blot and immunofluorescence were performed to detect PLK expression and phosphorylated PLK. Smooth Muscle Contractions were induced by electric field stimulation (EFS), α1-agonists, endothelin-1, or the thromboxane A2 analogue U46619 in organ bath. Results: RT-PCR, Western blot, and immunofluorescence suggested expression of PLK1 in the human prostate, which may be located and active in smooth Muscle cells. EFS-induced Contractions of prostate strips were reduced by SBE 13 (1 µM), cyclapolin 9 (3 µM), TAK 960 (100 nM), and Ro 3280 (100 nM). SBE 13 and cyclapolin 9 inhibited Contractions by the α1-agonists methoxamine, phenylephrine, and noradrenaline. In contrast, no effects of SBE 13 or cyclapolin 9 on endothelin-1- or U46619-induced Contractions were observed. Conclusions: Alpha1-adrenergic smooth Muscle Contraction in the human prostate can be inhibited by PLK inhibitors. PLK-dependent signaling may be a new pathway, which promotes α1-adrenergic Contraction of prostate smooth Muscle cells. As Contractions by endothelin and U46619 are not susceptible to PLK inhibition, this reflects divergent regulation of adrenergic and non-adrenergic prostate smooth Muscle Contraction.
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Inhibition of human prostate smooth Muscle Contraction by the LIM kinase inhibitors, SR7826 and LIMKi3.
British Journal of Pharmacology, 2018Co-Authors: Qingfeng Yu, Christian Gratzke, Annika Herlemann, Beata Rutz, Anna Ciotkowska, Christian Sterr, Frank Strittmatter, Yiming Wang, Xiaolong Wang, Christian G StiefAbstract:LUTS refer to a group of urological symptoms that are caused by multifactorial aetiology. The prevalence of LUTS increases with age, and will thereby lead to heavy economic burden for the society. In men with benign prostate hyperplasia, increased smooth Muscle tone in the prostate could result in bladder outlet obstruction and subsequent symptoms of lower urinary tract. Pharmacological treatment aiming to inhibit prostate smooth Muscle Contraction is considered as the option of first choice. However, the efficacy of current available treatment options is limited, thereby, improved understanding in the mechanisms of prostate smooth Muscle Contraction and development of novel targets for medical therapy are warranted. Previous studies have reported that LIMK (LIMK1 and LIMK2) phosphorylate cofilin and act as regulators of actin-myosin cytoskeletal dynamics, which result in actin polymerization, filament assemble, and stress fiber formation in smooth Muscle cells. This may suggest that LIMKs promote smooth Muscle Contraction, however, not any associated study has been conducted. In this project, we aimed to explore the effects of LIMK inhibitors on prostate smooth Muscle Contraction. Human prostate tissues were obtained from patients who underwent radical prostatectomy. RT-PCR, western blot and immunofluorescence were performed to detect LIMK in smooth Muscle cells of prostate tissues. Phosphorylation of cofilin, a LIMK substrate, was detected by a phospho-specific antibody. Effects of LIMK inhibitors on smooth Muscle Contraction of prostate strips were performed with organ bath. Expression of LIMK in smooth Muscle cells of prostate tissues was suggested by RT-PCR, Western blot and immunofluorescence, while higher expression level of LIMK was detected in prostate tissues than that in WPMY-1 cells. Two LIMK inhibitors, SR7826 (1 µM) and LIMKi3 (1 µM), showed significant effects on inhibiting Contractions of prostate strips, which were induced by the α1-adrenoceptor agonists, noradrenaline, phenylephrine and methoxamine, by the thromboxane A2 analogue, U46619, and by EFS. Reduced phosphorylation of cofilin in prostate tissues treated with inhibitors was observed, which confirmed LIMK inhibition by SR7826 and LIMKi3. In WPMY-1 cells, a line of cultured cells from the prostate stroma, SR7826 and LIMKi3 were observed to cause breakdown of actin filaments and reduced viability in a concentration-dependent manner. Together, this is the first study to explore the effects of small molecule LIMK inhibitors on regulating prostate smooth Muscle Contraction. The present study suggested that LIMKs promote prostate smooth Muscle Contraction by phosphorylating cofilin and subsequent causing actin organization, which could be inhibited by small molecule LIMK inhibitors, SR7826 and LIMKi3. Therefore, this project provides a possible novel therapy target for LUTS, although in vivo studies using animal models would be still warranted before clinical application.
