Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smooth muscle myosin heavy chains (MHCs), the motor proteins that power smooth muscle contraction, are produced by alternative splicing from a single gene. The smooth muscle MHC gene is capable of producing four isoforms by utilizing alternative splice sites located at the regions encoding the carboxy terminus and the junction of the 25- and 50-kDa tryptic peptides. These four isoforms, SM1A, SM1B, SM2A, and SM2B, are a combination of one of two heavy chains containing different carboxy-terminal tails (1 or 2) without (A) or with (B) an additional motif in the myosin head. In the present study, using RNA analysis and isoform-specific antibodies, we demonstrate the expression patterns of MHC isoforms during development in rat smooth muscle tissues. RNase protection analysis indicates that the mRNAs for SMA and SMB isoforms, which differ by a 21-nucleotide insertion in the region encoding the S1 head region of the myosin molecule, are differentially expressed during development in a highly tissue-specific manner. Smooth muscle MHC transcripts are first detectable in developing rat smooth muscle tissues at 17 days of fetal development. The SMB mRNA is shown to be expressed in smooth muscle from fetal bladder, intestine, and stomach and from neonatal aorta; however, it is not expressed in cultured smooth muscle cells from rat aorta. The SMA mRNA is also present at all stages of development in the smooth muscles examined; however, it is much less abundant than SMB mRNA in most fetal smooth muscles. We show here that the SMB isoform, which contains a unique seven-amino acid insertion at the junction of the 25- and 50-kDa tryptic peptides, is present in conjunction with SM1 and SM2 tails on immunoblots of smooth muscle from stomach, intestine, bladder, and uterus and is expressed during development in a pattern distinct from that of the SM1 and SM2 tail isoforms.
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PMID:Myosin heavy chain isoform expression in rat smooth muscle development. 968 13

Isolated single smooth muscle cells (SMCs) from different regions of the rabbit stomach were used to determine a possible correlation between unloaded shortening velocity and smooth muscle (SM) myosin heavy chain (MHC) S1 head isoform composition (SMA, no head insert; SMB, with head insert). alpha-Toxin-permeabilized isolated single cells were maximally activated to measure unloaded shortening velocity and subsequently used in an RT-PCR reaction to determine the SMA/SMB content of the same cell. SM MHC SMA and SMB isoforms are uniquely distributed in the stomach with cells from the fundic region expressing little SMB (38.1 +/- 7.3% SMB; n = 16); cells from the antrum express primarily SMB (94.9 +/- 1.0% SMB; n = 16). Mean fundic cell unloaded shortening velocity was 0.014 +/- 0.002 cell lengths/s compared with 0.036 +/- 0.002 for the antrum cells. Unloaded shortening velocity in these cells was significantly correlated with their percent SMB expression (r2 = 0.58). Resting cell length does not correlate with the percent SMB expression (n = 32 cells). Previously published assays of purified or expressed SMA and SMB heavy meromyosin show a twofold difference in actin filament sliding speed in in vitro motility assays. Extrapolation of our data to 0-100% SMB would give a 10-fold range of shortening velocity, which is closer to the approximately 20-fold range reported from various SM tissues. This suggests that mechanisms in addition to the MHC S1 head isoforms regulate shortening velocity.
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PMID:Single rabbit stomach smooth muscle cell myosin heavy chain SMB expression and shortening velocity. 1120 26

Cell transplantation has been proposed as a future therapy for various myocardial diseases. It is unknown, however, whether the encouraging results obtained in animal models of ischemia and reperfusion, cryoinjury or cardiomyopathy can be reproduced in the setting of permanent coronary artery occlusion and extensive myocardial infarction (MI). Embryonic cardiac cells were isolated and cultured for 3 days to confirm viability, morphology and to label cells with BrdU or the reporter gene LacZ. Seven days after extensive MI, rats were randomized to cell (1.5x10(6)) transplantation (n=11) or culture medium injection (n=16) into the myocardial scar. Echocardiography study was performed before and 53+/-3 days after implantation to assess left ventricular (LV) remodeling and function. During follow-up, there was no mortality among cell-treated rats v 4 of 16 control rats (P=0.12). X-gal staining, BrdU and alpha -SMA immunohistochemistry identified the engrafted cells 1 week, 4 weeks and 8 weeks after transplantation, respectively. Antibodies against alpha -SMA, connexin-43, fast and slow myosin heavy chain revealed grafts in various stages of differentiation in 10 of 11 cell-treated hearts. Many of them, however, kept their embryonic phenotype and were isolated from the host myocardium by scar tissue. Serial echocardiography studies revealed that cell transplantation prevented scar thinning, LV dilatation and dysfunction while control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. Transplantation of embryonic cardiomyocytes after extensive MI in a rat model attenuate LV dilatation, infarct thinning, and myocardial dysfunction. Still, many grafts remain isolated and do not differentiate into an adult phenotype, even when studied 2 months after grafting.
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PMID:Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. 1143 38

In smooth muscle cells (SMCs) isolated from rabbit carotid, femoral, and saphenous arteries, relative myosin isoform mRNA levels were measured in RT-PCR to test for correlations between myosin isoform expression and unloaded shortening velocity. Unloaded shortening velocity and percent smooth muscle myosin heavy chain 2 (SM2) and myosin light chain 17b (MLC(17b)) mRNA levels were not significantly different in single SMCs isolated from the luminal and adluminal regions of the carotid media. Saphenous artery SMCs shortened significantly faster (P < 0.05) than femoral SMCs and had more SM2 mRNA (P < 0.05) than carotid SMCs and less MLC(17b) mRNA (P < 0.001) and higher tissue levels of SMB mRNA (P < 0.05) than carotid and femoral SMCs. No correlations were found between percent SM2 and percent MLC(17b) mRNA levels and unloaded shortening velocity in SMCs from these arteries. We have previously shown that myosin heavy chain (MHC) SM1/SM2 and SMA/SMB and MLC(17a)/MLC(17b) isoform mRNA levels correlate with protein expression for these isoforms in rabbit smooth muscle tissues. Thus we interpret these results to suggest that 1) SMC myosin isoform expression and unloaded shortening velocity do not vary with distance from the lumen of the carotid artery but do vary in arteries located longitudinally within the arterial tree, 2) MHC SM1/SM2 and/or MLC(17a)/MLC(17b) isoform expression does not correlate with unloaded shortening velocity, and 3) intracellular expression of the MHC SM1/SM2 and MLC(17a)/MLC(17b) isoforms is not coregulated.
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PMID:Shortening velocity and myosin heavy- and light-chain isoform mRNA in rabbit arterial smooth muscle cells. 1194 May 25

We tested the hypothesis that sinusoidal length oscillation and receptor activation interactively regulate the abundance of mRNA encoding alpha-smooth muscle (alpha-SM) actin and myosin isoforms in intact bovine tracheal smooth muscle. We found that sinusoidal length oscillation significantly downregulated abundance of mRNA encoding alpha-SM actin mRNA in unstimulated tissues but not in histamine- and carbachol-activated tissues. This observation suggests antagonistic interactions between mechanical stretch and receptor-mediated signal transduction in regulating the abundance of mRNA encoding alpha-SM actin in intact airway smooth muscle. This pattern of antagonistic interaction was also observed in cholinergic receptor activation experiments. Whereas carbachol significantly upregulated myosin heavy chain SMA isoform expression in muscle strips held at slack length, carbachol did not significantly alter SMA expression in muscle strips at sinusoidal length oscillation. Carbachol also significantly upregulated GAPDH expression in bovine tracheal smooth muscle. However, unlike SMA expression, upregulation of GAPDH expression mediated by cholinergic receptor activation appeared to be insensitive to the mechanical state of airway smooth muscle. Unlike carbachol, histamine did not significantly alter the expression of GAPDH, myosin heavy chain SMA and SMB, myosin light chain LC17a and LC17b, and alpha-SM actin in bovine tracheal smooth muscle. U0126 (10 muM) completely inhibited carbachol-induced ERK1/2 MAPK phosphorylation but did not significantly affect carbachol-induced upregulation of GAPDH and SMA expression, suggesting that the ERK1/2 MAPK pathway was not the underlying mechanism. A potential implication of these findings is that periodic stretching of airways during respiratory cycles may modulate mRNA expression by receptor agonists in airway smooth muscle cells in vivo.
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PMID:Sinusoidal length oscillation- and receptor-mediated mRNA expression of myosin isoforms and alpha-SM actin in airway smooth muscle. 1531 64

The kinetics of smooth muscle are thought to be partially determined by the level of the expression of the 7 amino acid insert, SMB, in the myosin heavy chain, as SMB is generally expressed at higher levels in faster smooth muscle. In this study, we determined the role of this insert on shortening velocity and force regeneration following rapid reduction in muscle length (k(step)) in bladder tissue from a transgenic mouse line expressing the insert at three different levels: wild type (WT, +/+, SMB/SMB), an SMA homozygous type (SMB KO, -/-), and a heterozygous type (+/-, SMB/SMA). Smooth muscle from +/+ bladder shorten faster than both the +/- and -/- bladder smooth muscle when activated with Ca2+, consistent with SMB determining the shortening velocity of smooth muscle. The addition of Pi to the fully activated skinned bladder strips did not affect the rate of shortening for either the +/+ or -/- bladder types but did significantly decrease the rate of shortening for the +/- type. In contrast, the addition of ADP to fully Ca2+ activated bladder strips increased the rate of shortening for all three bladder types. However after thiophosphorylation, ADP slowed the shortening velocity. These data are consistent with shortening velocity being determined by the level of activation (or crossbridge attachment) in smooth muscle. The rates of force regeneration according to the k(step) protocol showed no differences between bladder types and also proved insensitive to either Pi or ADP. These data suggest that the rates of force regeneration were determined not only by the kinetics of the crossbridge cycle, but also by factors outside the contractile apparatus.
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PMID:Myosin heavy chain isoform expression regulates shortening velocity in smooth muscle: studies using an SMB KO mouse line. 1536 Jan 30

We investigated the impact of bone marrow-derived mesenchymal stem cells (BM-MSCs) alone or in combination with hepatocyte growth factor (HGF) transplantation via noninfarct-relative artery in a swine myocardial infarction (MI) model. Donor BM-MSCs were derived in vitro from swine auto-bone marrow cultures labeled by bromodeoxyuridine (BrdU) incorporation. Host MI swine model was created by ligating the distal left anterior descending artery. After 4 weeks, age-matched male MI swines were used for the transplantation. Male MI swines were transfused via noninfarct-relative artery with vehicle (control, n=6) or BrdU-labeled BM-MSCs (5 x 10(6)) alone (MSCs, n=6) or BrdU-labeled BM-MSCs (5 x 10(6)) combined with HGF (4 x 10(9) PFU) (MSCs+HGF, n=6). To evaluate the collateral artery growth (Rentrop) and cardiac perfusion in these animals, gate cardiac perfusion imaging and coronary angiography were performed before and 4 weeks after transplantation, respectively. To assess the contribution of donor-originated cells in stimulation of cardiomyocyte regeneration and angiogenesis, immunohistochemistry for BrdU and alpha-smooth muscle actin (alpha-SMA) and quantitative image analysis were performed at 4 weeks after transplantation. The results are as follows: (1) BrdU-positive cells were detected in host myocardium in both MSCs and MSCs+HGF groups, but not in the vehicle group. Most BrdU-positive cells expressed myosin heavy chain beta. (2) alpha-SMA(-)positive arteriole densities in the infarcted border area and infarcted area were increased significantly in both transplantation groups compared with the vehicle group. (3) Gate cardiac perfusion imaging demonstrated that the cardiac perfusion was significantly improved in transplantation groups compared with the vehicle group. (4) Ejection fraction and alpha-SMA-positive arteriole densities were increased significantly in both transplantation groups compared with the vehicle group. However, there was no difference in ejection fraction and alpha-SMA-positive arteriole densities between the MSCs group and the MSCs+HGF group. Growth of collateral arteries was not detected by coronary angiography in all three groups. In conclusion, the current study indicates that BM-MSCs transplantation via noninfarct-relative artery stimulates cardiomyocyte regeneration and angiogenesis and improves cardiac function, but does not stimulate collateral artery growth. BM-MSCs transplantation combined with HGF therapy is not superior to BM-MSCs alone transplantation. BM-MSCs transplantation via noninfarct-relative artery may be an alternative for those patients who cannot be transplanted via infarct-relative artery in clinical practice.
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PMID:Experimental study of bone marrow-derived mesenchymal stem cells combined with hepatocyte growth factor transplantation via noninfarct-relative artery in acute myocardial infarction. 1681 Jan 95

We previously developed a robust in vitro model system for vascular smooth muscle cell (VSMC) differentiation from neural crest cell line Monc-1 upon transforming growth factor-beta (TGF-beta) induction. Further studies demonstrated that both Smad and RhoA signaling are critical for TGF-beta-induced VSMC development. To identify downstream targets, we performed Affymetrix cDNA array analysis of Monc-1 cells and identified a gene named response gene to complement 32 (RGC-32) to be important for the VSMC differentiation. RGC-32 expression was increased 5-fold after 2 h and 50-fold after 24 h of TGF-beta induction. Knockdown of RGC-32 expression in Monc-1 cells by small interfering RNA significantly inhibited the expression of multiple smooth muscle marker genes, including SM alpha-actin (alpha-SMA), SM22alpha, and calponin. Of importance, the inhibition of RGC-32 expression correlated with the reduction of alpha-SMA while not inhibiting smooth muscle-unrelated c-fos gene expression, suggesting that RGC-32 is an important protein factor for VSMC differentiation from neural crest cells. Moreover, RGC-32 overexpression significantly enhanced TGF-beta-induced alpha-SMA, SM22alpha, and SM myosin heavy chain promoter activities in both Monc-1 and C3H10T1/2 cells. The induction of VSMC gene promoters by RGC-32 appears to be CArG-dependent. These data suggest that RGC-32 controls VSMC differentiation by regulating marker gene transcription in a CArG-dependent manner. Further studies revealed that both Smad and RhoA signaling are important for RGC-32 activation.
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PMID:Response gene to complement 32, a novel regulator for transforming growth factor-beta-induced smooth muscle differentiation of neural crest cells. 1732 22

Thromboxane A(2) (TxA(2)) is involved in smooth muscle contraction and atherosclerotic vascular diseases. Accumulating evidence suggests a pivotal role for mesenchymal stem cells (MSCs) in vascular remodeling. In the present study, we demonstrate for the first time that the TxA(2) mimetic U46619 induces differentiation of human adipose tissue-derived MSCs (hADSCs) to smooth muscle-like cells, as demonstrated by increased expression of smooth muscle-specific contractile proteins such as alpha-smooth muscle actin (alpha-SMA), calponin, smoothelin, and smooth muscle-myosin heavy chain. Using an in vitro collagen gel lattice contraction assay, we showed that U46619-induced expression of the contractile proteins was associated with increased contractility of the cells. U46619 increased the intracellular Ca(2+) concentration in hADSCs and pretreatment of the cells with the thromboxane receptor antagonist SQ29548 or the calmodulin (CaM) inhibitor W13 abrogated the U46619-induced alpha-SMA expression and contractility, suggesting a pivotal role of Ca(2+)/CaM in the U46619-stimulated smooth muscle differentiation of hADSCs. In addition, U46619 elicited activation of RhoA in hADSCs, and pretreatment of the cells with the Rho kinase-specific inhibitor Y27632 or overexpression of the dominant-negative mutants of RhoA and Rho kinase blocked U46619-stimulated alpha-SMA expression and contractility. Furthermore, U46619 induced phosphorylation of myosin light chain (MLC) through CaM/MLC kinase- and Rho kinase-dependent pathways, and the MLC kinase inhibitor ML-7 abrogated U46619-induced alpha-SMA expression and contractility. These results suggest that U46619 induces differentiation of hADSCs to contractile smooth muscle-like cells through CaM/MLCK- and RhoA-Rho kinase-dependent actin polymerization.
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PMID:Thromboxane a(2) induces differentiation of human mesenchymal stem cells to smooth muscle-like cells. 1884 63

Smooth muscle cells (SMCs) play an essential role in maintaining the structural and functional integrity of blood vessel and thus is a critical element for blood vessel construction via tissue engineering approach. Adipose-derived stem cells (ASCs) represent a reliable source of mesenchymal stem cells with multidifferentiation potential. In this study, the feasibility of differentiation of human ASCs (hASCs) into cells with phenotypic and functional properties of SMCs was explored. hASCs isolated from human lipoaspirate were expanded to passage 5 and then induced with administration of transforming growth factor-beta1 (TGF-beta1) and bone morphogenetic protein-4 (BMP4) either alone or in combination with culture medium. Expression of SMC-related markers including alpha-SM actin (alpha-SMA, SM22alpha, calponin, and SM myosin heavy chain) were detected by immunofluorescent staining, reverse transcription (RT)-polymerase chain reaction, and western blot analysis. It was found that only under the circumstance of a combined stimulation with TGF-beta1 and BMP4, both early and mid markers (alpha-SMA, SM22alpha, calponin) as well as a late marker (SM myosin heavy chain) of SMC differentiation were identified to similar levels as those in human umbilical artery SMCs. More importantly, these SM differentiated cells showed the function of contracting collagen matrix lattice when they were entrapped inside. The contractile function of differentiated hASCs was further enhanced by direct exposure to 60 mM KCl, consistent with what occurred in human umbilical artery SMCs. These results provide evidence that ASCs possess the potential to differentiate into contractile SM-like cells when stimulated by TGF-beta1 and BMP4 together. SMCs differentiated from hASCs may provide an abundant source as seed cells for blood vessel engineering.
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PMID:Differentiation of adipose-derived stem cells into contractile smooth muscle cells induced by transforming growth factor-beta1 and bone morphogenetic protein-4. 1989 5


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