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The Role of LIM Kinase in the Male Urogenital System
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750897/ https://www.ncbi.nlm.nih.gov/pubmed/35011645 http://dx.doi.org/10.3390/cells11010078 |
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author | Park, Juhyun Kim, Soo Woong Cho, Min Chul |
author_facet | Park, Juhyun Kim, Soo Woong Cho, Min Chul |
author_sort | Park, Juhyun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8750897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87508972022-01-12 The Role of LIM Kinase in the Male Urogenital System Park, Juhyun Kim, Soo Woong Cho, Min Chul Cells Review 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. MDPI 2021-12-28 /pmc/articles/PMC8750897/ /pubmed/35011645 http://dx.doi.org/10.3390/cells11010078 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Park, Juhyun Kim, Soo Woong Cho, Min Chul The Role of LIM Kinase in the Male Urogenital System |
title | The Role of LIM Kinase in the Male Urogenital System |
title_full | The Role of LIM Kinase in the Male Urogenital System |
title_fullStr | The Role of LIM Kinase in the Male Urogenital System |
title_full_unstemmed | The Role of LIM Kinase in the Male Urogenital System |
title_short | The Role of LIM Kinase in the Male Urogenital System |
title_sort | role of lim kinase in the male urogenital system |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750897/ https://www.ncbi.nlm.nih.gov/pubmed/35011645 http://dx.doi.org/10.3390/cells11010078 |
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