Noncoding RNAs in smooth muscle cell homeostasis: implications in phenotypic switch and vascular disorders

Coll-Bonfill, Núria; Cruz-Thea, Benjamin de la; Pisano, María Victoria; Musri, Melina M.

doi:10.1007/s00424-016-1821-x

Cited by 28 publications

(23 citation statements)

References 209 publications

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“…Taken together, these data indicate that miRNAs that initiate early-stage adipogenesis are mostly suppressed in mature adipocytes, but that many miRNAs that are involved in terminal differentiation remain highly abundant, which suggests that this miRNA cluster regulates varied cellular functions via distinct stages of the cell cycle. Such regulation is consistent with differentiation in other tissues, such as vascular smooth muscle cells, which undergo phenotypic switching that is mediated by several miRNA species that remain up-regulated after differentiation (44).…”

Section: Discussionsupporting

confidence: 79%

Impact of endurance exercise training on adipocyte microRNA expression in overweight men

et al. 2016

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Adipocytes are major regulators of metabolism, and endurance exercise training improves adipocyte function; however, the molecular mechanisms that regulate chronic adaptive responses remain unresolved. microRNAs (miRNAs) influence adipocyte differentiation and metabolism. Accordingly, we aimed to determine whether adipocyte miRNA expression is responsive to exercise training and to identify exercise-responsive miRNAs that influence adipocyte metabolism. Next-generation sequencing was used to profile miRNA expression of adipocytes that were isolated from abdominal subcutaneous (ABD) and gluteofemoral (GF) adipose tissue of overweight men before and after 6 wk of endurance exercise training. Differentially expressed miRNAs were overexpressed or silenced in 3T3-L1 adipocytes, and lipid metabolism was examined. Next-generation sequencing identified 526 miRNAs in adipocytes, and there were no statistical differences in miRNA expression when comparing pre- and post-training samples for ABD and GF adipocytes. miR-10b expression was increased in ABD compared with GF adipocytes, whereas miR-204, miR-3613, and miR-4532 were more highly expressed in GF compared with ABD adipocytes. Blocking miR-10b in adipocytes suppressed β-adrenergic lipolysis but generally had a minor effect on lipid metabolism. Thus, unlike their critical role in adipogenesis, stable changes in miRNA expression do not play a prominent role in the regulation of adipocyte function in response to endurance exercise training.-Tsiloulis, T., Pike, J., Powell, D., Rossello, F. J., Canny, B. J., Meex, R. C. R., Watt, M. J. Impact of endurance exercise training on adipocyte microRNA expression in overweight men.

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Section: Discussionsupporting

confidence: 79%

Impact of endurance exercise training on adipocyte microRNA expression in overweight men

et al. 2016

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“…This feature is common in vascular remodeling-associated diseases such as pulmonary hypertension (PH), chronic obstructive pulmonary disease (COPD), artheriosclerosis, aortic aneurysm and post-angioplasty restenosis [ 1 – 4 ], in which dedifferentiated SMC from the media translocate into the intima and proliferate [ 5 – 7 ]. The mechanisms mediating this phenomenon involve inflammation, shear stress, and hypoxia [ 4 , 8 , 9 , 10 ]. Dedifferentiated SMC that become proliferative and migratory, express more extracellular matrix components and fewer SMC contractile proteins [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Slug Is Increased in Vascular Remodeling and Induces a Smooth Muscle Cell Proliferative Phenotype

et al. 2016

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ObjectivePrevious studies have confirmed Slug as a key player in regulating phenotypic changes in several cell models, however, its role in smooth muscle cells (SMC) has never been assessed. The purpose of this study was to evaluate the expression of Slug during the phenotypic switch of SMC in vitro and throughout the development of vascular remodeling.Methods and ResultsSlug expression was decreased during both cell-to-cell contact and TGFβ1 induced SMC differentiation. Tumor necrosis factor-α (TNFα), a known inductor of a proliferative/dedifferentiated SMC phenotype, induces the expression of Slug in SMC. Slug knockdown blocked TNFα-induced SMC phenotypic change and significantly reduced both SMC proliferation and migration, while its overexpression blocked the TGFβ1-induced SMC differentiation and induced proliferation and migration. Genome-wide transcriptomic analysis showed that in SMC, Slug knockdown induced changes mainly in genes related to proliferation and migration, indicating that Slug controls these processes in SMC. Notably, Slug expression was significantly up-regulated in lungs of mice using a model of pulmonary hypertension-related vascular remodeling. Highly remodeled human pulmonary arteries also showed an increase of Slug expression compared to less remodeled arteries.ConclusionsSlug emerges as a key transcription factor driving SMC towards a proliferative phenotype. The increased Slug expression observed in vivo in highly remodeled arteries of mice and human suggests a role of Slug in the pathogenesis of pulmonary vascular diseases.

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“…However, under disease conditions such as atherosclerosis and hypertension, the phenotype of VSMCs shifts from contractile to synthetic, with an increased level of migration, proliferation and decreased contractile marker expression. Excessive proliferation of VSMCs and deposition of the ECM contribute to thickening of vessel walls and enhanced vascular stiffness [7,8]. At the molecular and cellular levels, vascular hyperreactivity, remodeling, and stiffening involve changes in cytoskeletal organization, cell-to-cell connections, cell growth, calcification, inflammation and rearrangement of VSMCs [9,10].…”

Section: Introductionmentioning

confidence: 99%

Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells

Xie

Shen

et al. 2020

ARCH BIOL SCI BELGRA

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Cytoglobin, a recently discovered globin, is expressed in vascular smooth muscle cells (VSMCs). Loss of cytoglobin provides a protective effect on vascular reconstruction but the effect of its overexpression is unclear. The aim of the study was to investigate the effect of cytoglobin overexpression on the migration and proliferation of VSMCs and possible mechanisms. We detected the expression of cytoglobin in hypertensive and normotensive rat aortas, with negative feedback regulation between cytoglobin and hypertension observed. The expression of cytoglobin was significantly decreased in hypertensive rats compared to normotensive rats, but VSMCs overexpressing cytoglobin displayed increased cell migration and proliferation, which led to a phenotypic switch. The increased expression of matrix metalloproteinase 9 and collagen Ia suggests a role for cytoglobin in extracellular matrix remodeling. Increased expression of proliferating cell nuclear antigen and decreased expression of p27 implies that cytoglobin is involved in modulating VSMC proliferation. Our findings indicate that cytoglobin may play an important role in vascular wall remodeling.

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Noncoding RNAs in smooth muscle cell homeostasis: implications in phenotypic switch and vascular disorders

Cited by 28 publications

References 209 publications

Impact of endurance exercise training on adipocyte microRNA expression in overweight men

Impact of endurance exercise training on adipocyte microRNA expression in overweight men

Slug Is Increased in Vascular Remodeling and Induces a Smooth Muscle Cell Proliferative Phenotype

Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells

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