Vascular smooth muscle cell differentiation – 2010

Miano, Joseph M.

doi:10.1016/s1674-8301(10)60026-7

Cited by 19 publications

(14 citation statements)

References 108 publications

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“…Therefore, because Klf4 binding to the CArG box and subsequent inhibition of SM-specific gene transcription is regulated by its relative abundance, high expression of the SM-specific genes is most often associated with low VSMC proliferation and migration rates whereas low expression of SM-specific genes is most often associated with high proliferation and migration rates. 23 miR-145 did not effect Klf5 expression in our study, nor did Klf5 change in response to RI suggesting that in contrast to Klf4, Klf5 does not play a role in VSMC phenotype regulation during CCG. Other studies have reported differential regulation of Klf4 and Klf5.…”

Section: Discussioncontrasting

confidence: 68%

MicroRNA-145 Restores Contractile Vascular Smooth Muscle Phenotype and Coronary Collateral Growth in the Metabolic Syndrome

Hutcheson

Terry

Chaplin

et al. 2013

ATVB

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Objective Transient, repetitive occlusion stimulates collateral growth (CCG) in normal animals. Vascular smooth muscle cells (VSMCs) switch to synthetic phenotype early in CCG then return to contractile phenotype. CCG is impaired in the metabolic syndrome. We determined whether impaired CCG was due to aberrant VSMC phenotypic modulation by miR-145-mediated mechanisms and if restoration of physiological miR-145 levels in metabolic syndrome (JCR rat) improved CCG. Approach/Results CCG was stimulated by transient, repetitive LAD occlusion and evaluated after 9 days by coronary blood flow measurements (microspheres). miR-145 was delivered to JCR VSMCs via adenoviral vector (miR-145-Adv). In JCR rats, miR-145 was decreased late in CCG (~2 fold day 6; ~4 fold day 9 vs. SD), which correlated with decreased expression of SM-specific contractile proteins (~5 fold day 6; ~10 fold day 9 vs. SD) indicative of VSMCs’ failure to return to the contractile phenotype late in CCG. miR-145 expression in JCR rats (miR-145-Adv) on days 6–9 of CCG completely restored VSMCs contractile phenotype and CCG (CZ/NZ flow ratio was 0.93±0.09 JCR+miR-145-Adv vs. 0.12±0.02 JCR vs. 0.87±0.02 SD). Conclusions Restoration of VSMC contractile phenotype through miR-145 delivery is a highly promising intervention for restoration of CCG in the metabolic syndrome.

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Section: Discussioncontrasting

confidence: 68%

MicroRNA-145 Restores Contractile Vascular Smooth Muscle Phenotype and Coronary Collateral Growth in the Metabolic Syndrome

Hutcheson

Terry

Chaplin

et al. 2013

ATVB

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“…There has been significant progress in understanding the hallmarks of the phenotypic modulation of SMC and the complex mechanisms involving the regulatory circuits of transcription factors and crosstalk of intracellular signalling pathways [1][2][3][4][5]. The main characteristics of differentiated SMC are the presence of a rich array of myofilaments and expression of a cytocontractile proteome that is necessary for the principal function of these cells, namely contraction.…”

Section: Discussionmentioning

confidence: 99%

“…Other established SMC differentiation marker proteins, namely smMHC, h-caldesmon [1][2][3][4] and dedifferentiation marker protein calmodulin [26], were also affected by changes in Tcadherin expression. Compared with their respective control E transductants Tcad+-SMC exhibited decreased levels of smMHC and h-caldesmon and elevated levels of calmodulin ( Fig.…”

Section: T-cadherin Upregulation Leads To Decay Of Smc Differentiatiomentioning

confidence: 98%

“…In the mature vessel SMC exhibit a differentiated phenotype characterized by the expression of a unique repertoire of contractile proteins, filaments and signalling molecules necessary for the regulation of the smooth muscle contractility. Unlike the majority of cells in the adult organism which are terminally differentiated, vascular SMC retain inherent plasticity even in the mature vessel and can undergo reversible changes in phenotype in response to changes in local environmental cues [1][2][3][4][5]. Loss of the differentiated phenotype, manifested as downregulation of contractile markers and acquisition of synthetic, migratory and proliferative properties, is important during vascular development and for reparation after vascular injury or remodelling in response to altered blood flow.…”

Section: Introductionmentioning

confidence: 99%

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T-cadherin promotes vascular smooth muscle cell dedifferentiation via a GSK3β-inactivation dependent mechanism

Frismantiene

Dasen

Pfaff

et al. 2016

Cellular Signalling

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Participation of the cadherin superfamily of adhesion molecules in smooth muscle cell (SMC) phenotype modulation is poorly understood. Immunohistochemical analyses of arterial lesions indirectly suggest upregulated expression of atypical glycosylphosphatidylinositol-anchored T-cadherin on vascular SMCs as a molecular indicator of the dedifferentiated/proliferative phenotype. This study investigated the role of T-cadherin in SMC phenotypic modulation. Morphological, molecular and functional SMC-signature characteristics of rat, porcine and human arterial SMCs stably transduced with respect to T-cadherin upregulation (Tcad+) or T-cadherin-deficiency (shTcad) were compared with their respective control transductants (E-SMCs or shC-SMCs). Tcad+-SMCs displayed several characteristics of the dedifferentiated phenotype including loss of spindle morphology, reduced/disorganized stress fiber formation, decay of SMC-differentiation markers (smooth muscle α-actin, smooth muscle myosin heavy chain, h-caldesmon), gain of SMC-dedifferentiation marker calmodulin, reduced levels of myocardin, nuclear-to-cytoplasmic redistribution of the myocardin related transcription factors MRTFA/B and increased proliferative and migratory capacities. T-cadherin depletion enforced features of the differentiated SMC phenotype. PI3K/Akt is a major signal pathway utilized by T-cadherin in SMCs and we investigated mTORC1/S6K1 and GSK3β axes as mediators of T-cadherin-induced dedifferentiation. Inhibition of mTORC1/S6K1 signalling by rapamycin suppressed proliferation in both E-SMCs and Tcad+-SMCs but failed to restore expression of contractile protein markers in Tcad+-SMCs. Ectopic adenoviral-mediated co-expression of constitutively active GSK3β mutant S9A in Tcad+-SMCs restored the morphological and molecular marker characteristics of differentiated SMCs and normalized rate of proliferation to that in control SMCs. In conclusion our study demonstrates that T-cadherin promotes acquisition of the dedifferentiated phenotype via a mechanism that is dependent on GSK3β inactivation.

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“…To determine whether PDGFRa þ cells represented a distinct population of interstitial cell, we performed double-label immunohistochemistry using antibodies against smooth muscle myosin II heavy chain (Smmhc), a specific marker for SMCs [34] and c-Kit, to identify ICCs, which are the pacemaker cells in the oviduct [26,35]. PDGFRa þ cells did not express considerable Smmhc, supported by a significant fold decrease in Myh11 expression in oviduct and uterus (Table 3), suggesting they were distinct from SMC in these organs.…”

Section: Peri Et Almentioning

confidence: 99%

A Novel Class of Interstitial Cells in the Mouse and Monkey Female Reproductive Tracts1

Peri¹,

Koh²,

Ward³

et al. 2015

Biology of Reproduction

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Growing evidence suggests important roles for specialized platelet-derived growth factor receptor alpha-positive (PDGFRalpha(+)) cells in regulating the behaviors of visceral smooth muscle organs. Examination of the female reproductive tracts of mice and monkeys showed that PDGFRalpha(+) cells form extensive networks in ovary, oviduct, and uterus. PDGFRalpha(+) cells were located in discrete locations within these organs, and their distribution and density were similar in rodents and primates. PDGFRalpha(+) cells were distinct from smooth muscle cells and interstitial cells of Cajal (ICC). This was demonstrated with immunohistochemical techniques and by performing molecular expression studies on PDGFRalpha(+) cells from mice with enhanced green fluorescent protein driven off of the endogenous promoter for Pdgfralpha. Significant differences in gene expression were found in PDGFRalpha(+) cells from ovary, oviduct, and uterus. Differences in gene expression were also detected in cells from different tissue regions within the same organ (e.g., uterine myometrium vs. endometrium). PDGFRalpha(+) cells are unlikely to provide pacemaker activity because they lack significant expression of key pacemaker genes found in ICC (Kit and Ano1). Gja1 encoding connexin 43 was expressed at relatively high levels in PDGFRalpha(+) cells (except in the ovary), suggesting these cells can form gap junctions to one another and neighboring smooth muscle cells. PDGFRalpha(+) cells also expressed the early response transcription factor and proto-oncogene Fos, particularly in the ovary. These data demonstrate extensive distribution of PDGFRalpha(+) cells throughout the female reproductive tract. These cells are a heterogeneous population of cells that are likely to contribute to different aspects of physiological regulation in the various anatomical niches they occupy.

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Vascular smooth muscle cell differentiation – 2010

Cited by 19 publications

References 108 publications

MicroRNA-145 Restores Contractile Vascular Smooth Muscle Phenotype and Coronary Collateral Growth in the Metabolic Syndrome

MicroRNA-145 Restores Contractile Vascular Smooth Muscle Phenotype and Coronary Collateral Growth in the Metabolic Syndrome

T-cadherin promotes vascular smooth muscle cell dedifferentiation via a GSK3β-inactivation dependent mechanism

A Novel Class of Interstitial Cells in the Mouse and Monkey Female Reproductive Tracts1

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