Changes in the expression and functional activities of Myosin II isoforms in human hyperplastic prostate

He, Weixiang; Wang, Xiao; Zhan, Daxing; Li, Mingzhou; Wang, Qian; Liu, Jianmin; Liu, Daoquan; Fu, Xun; Qian, Qiaofeng; Li, Yan; Chen, Ping; Zeng, Guang; Wang, Xinghuan; DiSanto, Michael E.; Zhang, Xinhua

doi:10.1042/cs20201283

Cited by 6 publications

(8 citation statements)

References 59 publications

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“…In addition, RhoA knockdown resulted in down-regulated expression of cytoskeletal components NMMHC-A and NMMHC-B. Previous studies had shown that NMMHC-A and NMMHC-B could promote proliferation and inhibit apoptosis of prostate cell lines (He et al 2021 ), their downregulation was therefore consistent with the observed proliferation and apoptosis trends.…”

Section: Discussionsupporting

confidence: 78%

Mechanism of RhoA regulating benign prostatic hyperplasia: RhoA-ROCK-β-catenin signaling axis and static & dynamic dual roles

Shan,

Su,

et al. 2023

Mol Med

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Background The pathogenesis of benign prostatic hyperplasia (BPH) has not been fully elucidated. Ras homology family member A (RhoA) plays an important role in regulating cell cytoskeleton, growth and fibrosis. The role of RhoA in BPH remains unclear. Methods This study aimed to clarify the expression, functional activity and mechanism of RhoA in BPH. Human prostate tissues, human prostate cell lines, BPH rat model were used. Cell models of RhoA knockdown and overexpression were generated. Immunofluorescence staining, quantitative real time PCR (qRT-PCR), Western blotting, cell counting kit-8 (CCK-8), flow cytometry, phalloidine staining, organ bath study, gel contraction assay, protein stability analysis, isolation and extraction of nuclear protein and cytoplasmic protein were performed. Results In this study we found that RhoA was localized in prostate stroma and epithelial compartments and was up-regulated in both BPH patients and BPH rats. Functionally, RhoA knockdown induced cell apoptosis and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transformation (EMT) and contraction. Consistently, overexpression of RhoA reversed all aforementioned processes. More importantly, we found that β-catenin and the downstream of Wnt/β-catenin signaling, including C-MYC, Survivin and Snail were up-regulated in BPH rats. Downregulation of RhoA significantly reduced the expression of these proteins. Rho kinase inhibitor Y-27632 also down-regulated β-catenin protein in a concentration-dependent manner. However, overexpression of β-catenin did not affect RhoA-ROCK levels, suggesting that β-catenin was the downstream of RhoA-ROCK regulation. Further data suggested that RhoA increased nuclear translocation of β-catenin and up-regulated β-catenin expression by inhibiting its proteasomal degradation, thereby activating Wnt/β-catenin signaling. Overexpression of β-catenin partially reversed the changes in cell growth, fibrosis and EMT except cell contraction caused by RhoA downregulation. Finally, Y-27632 partially reversed prostatic hyperplasia in vivo, further suggesting the potential of RhoA-ROCK signaling in BPH treatment. Conclusion Our novel data demonstrated that RhoA regulated both static and dynamic factors of BPH, RhoA-ROCK-β-catenin signaling axis played an important role in the development of BPH and might provide more possibilities for the formulation of subsequent clinical treatment strategies.

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Section: Discussionsupporting

confidence: 78%

Mechanism of RhoA regulating benign prostatic hyperplasia: RhoA-ROCK-β-catenin signaling axis and static & dynamic dual roles

Shan,

Su,

et al. 2023

Mol Med

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“…As previously reported [12,16,18], the differences in nucleic acid sequence in each pair of SMM isoforms were quite small. Because of this, competitive RT-PCR was used to detect the expression of SMM isoforms.…”

Section: Competitive Rt-pcrsupporting

confidence: 74%

“…Previously, we collected human hyperplastic prostate tissues from 10 patients undergoing radical cystectomy and found that hyperplasia prostate SM expressed more MHC, NMMHC-A, and NMMHC-B when compared to normal prostate tissues [16]. In this study, as shown in Figure 1, the inclusion criteria were extended, and we included 30 BPH patients who sought surgical treatment for moderate-to-severe LUTSs secondary to BPO or acute/chronic urine retention.…”

Section: Introductionmentioning

confidence: 99%

Alteration of the Expression and Functional Activities of Myosin II Isoforms in Enlarged Hyperplastic Prostates

Wang,

He,

Chen

et al. 2024

JPM

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Introduction: Benign prostatic hyperplasia (BPH) is a common pathologic process in aging men, and the contraction of the prostatic smooth muscles (SMs) in the stroma plays a vital role in this pathogenesis, leading to lower urinary tract symptoms (LUTSs). The isoforms of both the SM myosin (SMM) and non-muscle myosin (NMM) are associated with the contraction type of the prostatic SMs, but the mechanism has not been fully elucidated. Methods: We collected prostate tissues from 30 BPH patients receiving surgical treatments, and normal human prostate samples were obtained from 12 brain-dead men. A testosterone-induced (T-induced) rat model was built, and the epithelial hyperplastic prostates were harvested. Competitive RT-PCR was used to detect the expression of SMM isoforms. We investigated the contractility of human prostate strips in vitro in an organ bath. Results: The results regarding the comparisons of SMM isoforms varied between rat models and human samples. In comparison with T-induced rats and controls, competitive RT-PCR failed to show any statistically significant difference regarding the compositions of SMM isoforms. For human prostates samples, BPH patients expressed more SM-1 isoforms (66.8% vs. 60.0%, p < 0.001) and myosin light chain-17b (MLC17b) (35.9% vs. 28.5%, p < 0.05) when compared to young donors. There was a significant decrease in prostate myosin heavy chain (MHC) expression in BPH patients, with a 66.4% decrease in MHC at the mRNA level and a 51.2% decrease at the protein level. The upregulated expression of non-muscle myosin heavy chain-B (NMMHC-B) was 1.6-fold at the mRNA level and 2.1-fold at the protein level. The organ bath study showed that isolated prostate strips from BPH patients produced slower tonic contraction compared to normal humans. Conclusion: In this study, we claim that in the enlarged prostates of patients undergoing surgeries, MHC expression significantly decreased compared to normal tissues, with elevated levels of SM-1, MLC17b, and NMMHC-B isoforms. Modifications in SMM and NMM might play a role in the tonic contractile properties of prostatic SMs and the development of LUTS/BPH. Understanding this mechanism might provide insights into the origins of LUTS/BPH and facilitate the identification of novel therapeutic targets.

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“…Cell lines obtained and cultured, CCK-8 assay, total RNA extraction, RNA reverse transcription, qRT-PCR analysis, Western blot analysis, hematoxylin and eosin (H&E) staining and masson’s trichrome staining analysis were performed as we previously described [ 35 , 36 ]. Primer sequences were summarized in Additional file 1 : Table S1.…”

Section: Methodsmentioning

confidence: 99%

Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK /ERK1/2 pathway and resisted autophagy-related ferroptosis via AMPK/mTOR pathway in hyperplastic prostate

Li,

Zhou,

Liu

et al. 2023

J Transl Med

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Background Benign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH. Methods Human prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson’s trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments. Results Our study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations. Conclusions Our novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.

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Changes in the expression and functional activities of Myosin II isoforms in human hyperplastic prostate

Cited by 6 publications

References 59 publications

Mechanism of RhoA regulating benign prostatic hyperplasia: RhoA-ROCK-β-catenin signaling axis and static & dynamic dual roles

Mechanism of RhoA regulating benign prostatic hyperplasia: RhoA-ROCK-β-catenin signaling axis and static & dynamic dual roles

Alteration of the Expression and Functional Activities of Myosin II Isoforms in Enlarged Hyperplastic Prostates

Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK /ERK1/2 pathway and resisted autophagy-related ferroptosis via AMPK/mTOR pathway in hyperplastic prostate

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