scholarly journals Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations

2021 ◽  
Author(s):  
Ryo Maekawa ◽  
Shun Sato ◽  
Tetsuro Tamehisa ◽  
Takahiro Sakai ◽  
Takuya Kajimura ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Uterine Fibroids ◽  
Muscle Cells ◽  
Histological Features ◽  
Dna Methylome

Abstract Background: Somatic mutations in Mediator complex subunit 12 (MED12m) have been reported as a biomarker of uterine fibroids (UFs). However, the role of MED12m is still unclear in the pathogenesis of UFs. Therefore, we investigated the differences in DNA methylome, transcriptome, and histological features between MED12m-positive and -negative UFs. Methods: DNA methylomes and transcriptomes were obtained from MED12m-positive and -negative UFs and myometrium, and hierarchically clustered. Differentially expressed genes in comparison with the myometrium and co-expressed genes detected by weighted gene co-expression network analysis were subjected to gene ontology enrichment analyses. The amounts of collagen fibers and the number of blood vessels and smooth muscle cells were histologically evaluated. Results: Hierarchical clustering based on DNA methylation clearly separated the myometrium, MED12m-positive, and MED12m-negative UFs. MED12m-positive UFs had the increased activities of extracellular matrix formation, whereas MED12m-negative UFs had the increased angiogenic activities and smooth muscle cell proliferation. Conclusion: The MED12m-positive and -negative UFs had different DNA methylation, gene expression, and histological features. The MED12m-positive UFs form the tumor with a rich extracellular matrix and poor blood vessels and smooth muscle cells compared to the MED12m-negative UFs, suggesting MED12 mutations affect the tissue composition of UFs.

scholarly journals Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction

2008 ◽  
Vol 295 (3) ◽  
pp. C576-C587 ◽  
Author(s):  
Susan J. Gunst ◽  
Wenwu Zhang
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Actin Polymerization ◽  
Muscle Cells ◽  
Smooth Muscle Contraction ◽  
Mechanical Tension ◽  
Muscle Tissues ◽  
Cytoskeletal Dynamics

A growing body of data supports a view of the actin cytoskeleton of smooth muscle cells as a dynamic structure that plays an integral role in regulating the development of mechanical tension and the material properties of smooth muscle tissues. The increase in the proportion of filamentous actin that occurs in response to the stimulation of smooth muscle cells and the essential role of stimulus-induced actin polymerization and cytoskeletal dynamics in the generation of mechanical tension has been convincingly documented in many smooth muscle tissues and cells using a wide variety of experimental approaches. Most of the evidence suggests that the functional role of actin polymerization during contraction is distinct and separately regulated from the actomyosin cross-bridge cycling process. The molecular basis for the regulation of actin polymerization and its physiological roles may vary in diverse types of smooth muscle cells and tissues. However, current evidence supports a model for smooth muscle contraction in which contractile stimulation initiates the assembly of cytoskeletal/extracellular matrix adhesion complex proteins at the membrane, and proteins within this complex orchestrate the polymerization and organization of a submembranous network of actin filaments. This cytoskeletal network may serve to strengthen the membrane for the transmission of force generated by the contractile apparatus to the extracellular matrix, and to enable the adaptation of smooth muscle cells to mechanical stresses. Better understanding of the physiological function of these dynamic cytoskeletal processes in smooth muscle may provide important insights into the physiological regulation of smooth muscle tissues.

scholarly journals EPAC in Vascular Smooth Muscle Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5160 ◽  
Author(s):  
Nadine Wehbe ◽  
Suzanne Awni Nasser ◽  
Yusra Al-Dhaheri ◽  
Rabah Iratni ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Tone ◽  
Muscle Cells ◽  
Effector Proteins ◽  
Phenotypic Switching

Vascular smooth muscle cells (VSMCs) are major components of blood vessels. They regulate physiological functions, such as vascular tone and blood flow. Under pathological conditions, VSMCs undergo a remodeling process known as phenotypic switching. During this process, VSMCs lose their contractility and acquire a synthetic phenotype, where they over-proliferate and migrate from the tunica media to the tunica interna, contributing to the occlusion of blood vessels. Since their discovery as effector proteins of cyclic adenosine 3′,5′-monophosphate (cAMP), exchange proteins activated by cAMP (EPACs) have been shown to play vital roles in a plethora of pathways in different cell systems. While extensive research to identify the role of EPAC in the vasculature has been conducted, much remains to be explored to resolve the reported discordance in EPAC’s effects. In this paper, we review the role of EPAC in VSMCs, namely its regulation of the vascular tone and phenotypic switching, with the likely involvement of reactive oxygen species (ROS) in the interplay between EPAC and its targets/effectors.

scholarly journals Dynamic Crosstalk between Vascular Smooth Muscle Cells and the Aged Extracellular Matrix

2021 ◽  
Vol 22 (18) ◽  
pp. 10175
Author(s):  
Joao Carlos Ribeiro-Silva ◽  
Patricia Nolasco ◽  
Jose Eduardo Krieger ◽  
Ayumi Aurea Miyakawa
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Elastic Fibers ◽  
Signaling Mechanisms ◽  
Arterial Aging ◽  
Underlying Mechanisms ◽  
Cell Phenotypes

Vascular aging is accompanied by the fragmentation of elastic fibers and collagen deposition, leading to reduced distensibility and increased vascular stiffness. A rigid artery facilitates elastin to degradation by MMPs, exposing vascular cells to greater mechanical stress and triggering signaling mechanisms that only exacerbate aging, creating a self-sustaining inflammatory environment that also promotes vascular calcification. In this review, we highlight the role of crosstalk between smooth muscle cells and the vascular extracellular matrix (ECM) and how aging promotes smooth muscle cell phenotypes that ultimately lead to mechanical impairment of aging arteries. Understanding the underlying mechanisms and the role of associated changes in ECM during aging may contribute to new approaches to prevent or delay arterial aging and the onset of cardiovascular diseases.

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