Disease relevance of Acta2

• Thus, smooth muscle alpha-actin is a molecular marker of the presence and extent of pressure-overload hypertrophy, whose correlation with cardiac growth at least equals that of skeletal alpha-actin [1].
• The vascular smooth muscle alpha-actin gene is reactivated during cardiac hypertrophy provoked by load [1].
• Stellate cells, the primary extracellular matrix-producing cells in the liver, undergo activation characterized by fibrogenesis, proliferation and smooth muscle alpha-actin expression, in hepatic fibrosis or when cultured on plastic [2].
• Gene transfer with smooth muscle alpha actin into the SR-3Y1-2 cell line reduced growth and invasiveness in vitro, as well as tumor growth and experimental lung metastasis depending on the expression of the alpha actin [3].
• Human malignant melanoma cells release a factor that inhibits the expression of smooth muscle alpha-actin [4].

High impact information on Acta2

• In cultured stellate cells, ET-1 and sarafotoxin S6C (a potent ETB receptor agonist) stimulated stellate cell activation, as assessed by expression of smooth muscle alpha-actin [5].
• Hepatic wounding is characterized by the "activation" of resident stellate cells (lipocytes, Ito cells) to myofibroblast-like cells that produce increased amounts of smooth muscle alpha-actin and extracellular matrix [5].
• In freshly isolated stellate cells from injured livers, bosentan reduced expression of activation markers, including smooth muscle alpha-actin and extracellular matrix mRNAs [5].
• In culture, lipocytes became contractile only after spreading and activating, coincident with expression of smooth muscle alpha actin, a marker of activation (1990. Virchows Arch. B Cell Pathol. 59:349) [6].
• These include the gene encoding vascular smooth muscle alpha-actin, the earliest alpha-actin expressed during cardiac myogenesis; however, it is not known whether reactivation of the smooth muscle alpha-actin gene occurs in ventricular hypertrophy [1].

Chemical compound and disease context of Acta2

• During induction of fibrosis by carbon tetrachloride, nestin-positive stellate cells appeared at 6 weeks, which was late in comparison with the induction of desmin and smooth muscle alpha-actin [7].
• Prolonged exposure of vascular smooth muscle cells (VSMC) to vasoconstrictors such as vasopressin or angiotensin II induces hypertrophy and increases expression of muscle-specific genes including smooth muscle alpha-actin (SM-alpha-actin) [8].
• Moreover, Y-27632 reduced the number of smooth muscle alpha-actin- and transforming growth factor beta1-positive cells, and inhibited the expression of Na(+)/Ca(2+) exchanger mRNA which was reported to be an indicator of HSCs activation and liver fibrosis [9].

Biological context of Acta2

• The expression of smooth muscle alpha-actin (Acta2, which we abbreviate as alpha-SM-actin) and gamma-actin mRNAs and proteins was examined by real-time polymerase chain reaction and Western immunoblot, and was localized with immunohistochemistry, in the nonpregnant, pregnant, and postpartum rat uterus [10].
• Expression of vascular smooth muscle alpha-actin, the earliest alpha-actin induced during cardiac myogenesis, was increased by all three growth factors [11].
• The nucleotide sequence of a rat vascular smooth muscle alpha-actin cDNA [12].
• Induction of smooth muscle alpha-actin was delayed and sustained after aortic constriction, whereas the nuclear oncogenes c-jun and junB were expressed rapidly and transiently, providing potential dimerization partners for transcriptional control by c-fos [1].
• Ventricular mass after 2 d or more of aortic constriction was more highly correlated with smooth muscle alpha-actin gene activation (r = 0.852; P = 0.0001) than with skeletal muscle alpha-actin (r = 0.532; P = 0.009); P less than 0.0005 for the difference in the correlation coefficients [1].

Anatomical context of Acta2

• Evidence for the presence of smooth muscle alpha-actin within pericytes of the renal medulla [13].
• Whereas lipocytes from normal liver were initially compact, smooth muscle alpha actin negative and noncontractile, cells from animals with hepatic injury due to CCl4 displayed an activated appearance, expressed smooth muscle alpha actin, and were contractile immediately after adherence [6].
• In hypertrophied hearts, the prevalence of smooth muscle alpha-actin gene induction was 0.909, versus 0.545 for skeletal muscle alpha-actin (P less than 0.05) [1].
• Cell cycle versus density dependence of smooth muscle alpha actin expression in cultured rat aortic smooth muscle cells [14].
• Furthermore, the fact that Ang II and AVP induced selective increases in smooth muscle alpha-actin suggests that these agonists may not only regulate growth of vascular smooth muscle but may also promote expression of smooth muscle-specific contractile proteins during differentiation of vascular smooth muscle [15].

Associations of Acta2 with chemical compounds

• Angiotensin II-induced stimulation of smooth muscle alpha-actin expression by serum response factor and the homeodomain transcription factor MHox [16].
• TGF beta, but not retinoic acid, diminished PDGF-receptor and smooth-muscle alpha-actin abundance [17].
• Moreover, in ET-1+ISO-treated heart tissues, reprogramming of gene expression was observed with an increased ratio of beta-myosin heavy chain (MHC) to alpha-MHC mRNA and increased transcript levels of ANF and skeletal/smooth muscle alpha-actin isoforms [18].
• Tranilast decreased DNA synthesis and increased smooth muscle alpha-actin expression. mRNA expressions of procollagen and TGF beta 1 were reduced by tranilast [2].
• Regulation of smooth muscle alpha-actin promoter by vasopressin and platelet-derived growth factor in rat aortic vascular smooth muscle cells [19].

Regulatory relationships of Acta2

• Four days after injury, TGF-beta R:Fc treatment almost completely inhibited the induction of smooth muscle alpha-actin expression in adventitial cells [20].
• In the neointima, elastin mRNA-expressing cells do not stain with antibodies to either smooth muscle alpha-actin or macrophage proteins [21].
• At the same time, IGF-I suppressed the accumulation of smooth muscle alpha-actin (sm-alpha-actin) in a dose-dependent manner [22].

Other interactions of Acta2

• Expression of smooth muscle alpha-actin was specific to the descending vasa recta and not a result of tubular contamination because RT-PCR amplification of the vasopressin V2 receptor, which is a specific tubular marker, did not occur [13].
• Increases in actin content were due largely to increased expression of smooth muscle alpha-actin (3.6- to 7.5-fold), as opposed to nonmuscle beta-actin (1.7- to 2.5-fold) [15].
• Induction of smooth muscle alpha-actin in vascular smooth muscle cells by arginine vasopressin is mediated by c-Jun amino-terminal kinases and p38 mitogen-activated protein kinase [23].
• Similarities and differences in smooth muscle alpha-actin induction by TGF-beta in smooth muscle versus non-smooth muscle cells [24].
• In the present study we examined the changes in a number of smooth muscle differentiation markers including smooth muscle alpha-actin and myosin, vinculin, desmin, laminin and vimentin as well as changes in fine structure by electron microscopy [25].

Analytical, diagnostic and therapeutic context of Acta2

• Extraction of total RNA from microdissected outer medullary descending vasa recta allowed for the detection of smooth muscle alpha-actin mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR) [13].
• Immunofluorescence confirmed that smooth muscle alpha-actin is localized at the surface of nonpermeabilized CPAE cells [26].
• Immunoblotting with a specific smooth muscle alpha-actin antibody detected the presence of this type of actin among the isolated cell surface proteins [26].
• Allografts were removed on days 2-10 (n=13), 30 (n=4), and 60 (n=5) for histology, computerized morphometry (obliteration), and immunohistochemical detection of mononuclear cells, smooth muscle alpha-actin, and tissue phenotype [27].
• When these cells were cultured on plastic dishes for 3 days, they showed marked DNA synthesis and smooth muscle alpha actin and TGF-beta mRNA expressions assessed by (3)H-thymidine incorporation and Northern blotting, respectively [28].

References