scholarly journals Proliferation precedes differentiation in IGF-I-stimulated myogenesis.

1996 ◽  
Vol 135 (2) ◽  
pp. 431-440 ◽  
Author(s):  
J C Engert ◽  
E B Berglund ◽  
N Rosenthal
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Myogenic Differentiation ◽  
Transcript Accumulation ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Subsequent Activation ◽  
Myogenic Factors ◽  
Stimulation Of ◽  
Insulin Like Growth Factors

The insulin-like growth factors (IGFs) have dramatic and complex effects on the growth of many tissues and have been implicated in both the proliferation and differentiation of skeletal muscle cells. A detailed analysis of gene expression was performed in L6E9 myoblast cultures treated with IGF-I to dissect the early events leading to the stimulation of myogenic differentiation by this growth factor. A time course of transcript accumulation in confluent L6E9 myoblasts treated with defined media containing IGF-I revealed an initial transient decrease in myogenic factors, accompanied by an increase in cell cycle markers and cell proliferation. This pattern was reversed at later time points, when the subsequent activation of myogenic factors resulted in a net increase in structural gene expression and larger myotubes. The data presented here support the hypothesis that IGF-I activates proliferation first, and subsequently stimulates events leading to the expression of muscle-specific genes in myogenic cell cultures.

Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue

1992 ◽  
Vol 263 (4) ◽  
pp. E637-E645 ◽  
Author(s):  
C. K. Wolverton ◽  
M. J. Azain ◽  
J. Y. Duffy ◽  
M. E. White ◽  
T. G. Ramsay
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Dietary Fat ◽  
Subcutaneous Adipose Tissue ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Systemic Factors ◽  
Subcutaneous Adipose ◽  
Acid Esterification

The present study was designed to evaluate the effects of porcine somatotropin (pST) treatment (2 mg/day) and dietary fat (10%) separately and in combination on the metabolic activity of subcutaneous adipose tissue, serum adipogenic activity, and insulin-like growth factor (IGF) gene expression within adipose tissue from growing 5- to 6-mo-old barrows. This study attempted to determine how these factors might contribute to the reported changes in adiposity of treated swine. Biopsies of adipose tissue were collected after 28 days of treatment following anesthesia with thiopental sodium (15 mg/kg iv). Somatotropin inhibited in vitro glucose oxidation and lipogenesis in adipose tissue but did not affect fatty acid esterification. Adipogenic activity of serum was not altered by pST treatment. Subcutaneous adipose tissue contained mRNA for IGF-I and -II, and pST administration increased the abundance of IGF-I mRNA. Dietary fat had no effect on these variables. Thus somatotropin reduces glucose metabolism in porcine subcutaneous adipose tissue. Preadipocyte proliferation and differentiation are not affected by somatotropin through its actions on systemic factors. Dietary fat provides no additional benefit in combination with pST administration to affect accretion of adipose tissue in growing swine.

scholarly journals Loss of IGF-IEa or IGF-IEb Impairs Myogenic Differentiation

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1923-1934 ◽  
Author(s):  
Ronald W. Matheny ◽  
Bradley C. Nindl
Keyword(s):  
Splice Variants ◽  
Myogenic Differentiation ◽  
Horse Serum ◽  
Myoblast Differentiation ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Simultaneous Loss ◽  
Functional Relevance ◽  
Free Media ◽  
The Impact

Actions of protein products resulting from alternative splicing of the Igf1 gene have received increasing attention in recent years. However, the significance and functional relevance of these observations remain poorly defined. To address functions of IGF-I splice variants, we examined the impact of loss of IGF-IEa and IGF-IEb on the proliferation and differentiation of cultured mouse myoblasts. RNA interference-mediated reductions in total IGF-I, IGF-IEa alone, or IGF-IEb alone had no effect on cell viability in growth medium. However, cells deficient in total IGF-I or IGF-IEa alone proliferated significantly slower than control cells or cells deficient in IGF-IEb in serum-free media. Simultaneous loss of both or specific loss of either splice variant significantly inhibited myosin heavy chain (MyHC) immunoreactivity by 70–80% (P < 0.01) under differentiation conditions (48 h in 2% horse serum) as determined by Western immunoblotting. This loss in protein was associated with reduced MyHC isoform mRNAs, because reductions in total IGF-I or IGF-IEa mRNA significantly reduced MyHC mRNAs by approximately 50–75% (P < 0.05). Loss of IGF-IEb also reduced MyHC isoform mRNA significantly, with the exception of Myh7, but to a lesser degree (∼20–40%, P < 0.05). Provision of mature IGF-I, but not synthetic E peptides, restored Myh3 expression to control levels in cells deficient in IGF-IEa or IGF-IEb. Collectively, these data suggest that IGF-I splice variants may regulate myoblast differentiation through the actions of mature IGF-I and not the E peptides.

scholarly journals Identification of a cDNA from the Arbuscular Mycorrhizal Fungus Glomus intraradices that is Expressed During Mycorrhizal Symbiosis and Up-Regulated by N Fertilization

2002 ◽  
Vol 15 (4) ◽  
pp. 360-367 ◽  
Author(s):  
Juan M. Ruiz-Lozano ◽  
Carlos Collados ◽  
Rosa Porcel ◽  
Rosario Azcón ◽  
JoséM. Barea
Keyword(s):  
Gene Expression ◽  
Gene Product ◽  
Time Course ◽  
Glomus Intraradices ◽  
Mycorrhizal Fungus ◽  
Arbuscular Mycorrhizal ◽  
N Fertilization ◽  
Mycorrhizal Symbiosis ◽  
Transcript Accumulation ◽  
Reading Frame

A cDNA library was constructed with RNA from Glomus intraradices-colonized lettuce roots and used for differential screening. This allowed the identification of a cDNA (Gi-1) that was expressed only in mycorrhizal roots and was of fungal origin. The function of the gene product is unknown, because Gi-1 contained a complete open reading frame that was predicted to encode a protein of 157 amino acids which only showed little homology with glutamine synthetase from Helicobacter pylori. The time-course analysis of gene expression during the fungal life cycle showed that Gi-1 was expressed only during the mycorrhizal symbiosis and was not detected in dormant or germinating spores of G. intraradices. P fertilization did not significantly change the pattern of Gi-1 expression compared with that in the unfertilized treatment, whereas N fertilization (alone or in combination with P) considerably enhanced the Gi-1 transcript accumulation. This increase in gene expression correlated with plant N status and growth under such conditions. The possible role of the Gi-1 gene product in intermediary N metabolism of arbuscular mycorrhizal symbiosis is further discussed.

scholarly journals Glucose-Regulated Protein 94 (GRP94): A Novel Regulator of Insulin-Like Growth Factor Production

2020 ◽  
Author(s):  
Yair Argon ◽  
Sophie E. Bresson ◽  
Michal T. Marzec ◽  
Adda Grimberg
Keyword(s):  
Gene Expression ◽  
Metabolic Diseases ◽  
Somatic Growth ◽  
Cellular Responses ◽  
Chaperone Protein ◽  
Igf I ◽  
Growth Factor Production ◽  
Novel Target ◽  
Glucose Regulated Protein ◽  
Insulin Like Growth Factors

Mammals have two insulin-like growth factors (IGF) that are key mediators of somatic growth, of tissue differentiation and cellular responses to stress. Thus, the mechanisms that regulate the bioavailability of IGFs are important in both normal and aberrant development. IGF-I levels are primarily controlled via the growth hormone-IGF axis, in response to nutritional status, and also reflect metabolic diseases and cancer. One mechanism that controls IGF bioavailablity is the binding of circulating IGF to a number of binding proteins that keep IGF in a stable, but receptor non-binding state. But even before IGF is released from the cells that produce it, it undergoes an obligatory association with a ubiquitous chaperone protein, GRP94. This binding is required for secretion of a properly folded, mature IGF. This chapter reviews the known aspects of the interaction and highlights the specificity issues yet to be determined. The IGF-GRP94 interaction provides a potential novel mechanism of idiopathic short stature, involving the obligatory chaperone and not just IGF gene expression. It also provides a novel target for cancer treatment, as GRP94 activity can be either inhibited or enhanced.

Developmental regulation of creatine kinase gene expression by myogenic factors in embryonic mouse and chick skeletal muscle

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 1017-1029 ◽  
Author(s):  
G.E. Lyons ◽  
S. Muhlebach ◽  
A. Moser ◽  
R. Masood ◽  
B.M. Paterson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Striated Muscle ◽  
Myogenic Differentiation ◽  
Developmental Regulation ◽  
Specific Gene ◽  
Kinase Gene ◽  
Embryonic Mouse ◽  
Myogenic Factors

The B isoform of creatine kinase (BCK), which is expressed at a high level in embryonic neural tissues, is also expressed abundantly in developing striated muscle and is an early marker for skeletal myogenesis. Using isoform-specific 35S-labeled antisense cRNA probes for in situ hybridization, we have detected BCK mRNAs in embryonic mouse and chick myotomes, the first skeletal muscle masses to form in developing embryos. These transcripts are detectable as soon as myotomes are morphologically distinguishable. BCK is expressed at high levels in both skeletal and cardiac muscle in mouse and chick embryos. In the mouse, BCK transcript levels fall of rapidly in striated muscle shortly after the onset of MCK gene expression. The M isoform of creatine kinase (MCK), the striated muscle-specific isoform, is expressed later than BCK. In the mouse, BCK transcripts are expressed in myotomes at 8.5 days post coitum (p.c.), but MCK transcripts are not detected before 13 days p.c. In the chick, BCK mRNAs are present at Hamburger-Hamilton stage 13, but MCK mRNAs are not detected before stage 19. We have compared the patterns of expression of the CK genes with those of myogenic differentiation factor genes, which are thought to regulate skeletal muscle-specific gene expression. In the chick, both CMD1, first detected at stage 13, and myogenin, first detected at stage 15, are present prior to MCK, which begins to be expressed at stage 19. Unlike the mouse embryo, CMD1, the chick homologue of MyoD1, is expressed before chick myogenin. In the mouse, myogenin, first detected at 8.5 days p.c., is expressed at the same time as BCK in myotomes. Both myogenin and MyoD1, which begins to be detected two days later than myogenin, are expressed at least two days before MCK. It has been proposed that the myogenic factors, MyoD1 and myogenin, directly regulate MCK gene expression in the mouse by binding to its enhancer. However, our results show that MCK transcripts are not detected until well after MyoD1 and myogenin mRNAs are expressed, suggesting that these factors by themselves are not sufficient to initiate MCK gene expression.

scholarly journals Temporal microRNA expression during in vitro myogenic progenitor cell proliferation and differentiation: regulation of proliferation by miR-682

2011 ◽  
Vol 43 (10) ◽  
pp. 621-630 ◽  
Author(s):  
Yongxin Chen ◽  
Jonathan Gelfond ◽  
Linda M. McManus ◽  
Paula K. Shireman
Keyword(s):  
Gene Expression ◽  
Mirna Expression ◽  
Muscle Regeneration ◽  
Progenitor Cell ◽  
Time Course ◽  
Differentially Expressed ◽  
Proliferation And Differentiation ◽  
Myogenic Progenitor

MicroRNAs (miRNAs) regulate gene expression by repressing target genes at the posttranscriptional level. Since miRNAs have unique expression profiles in different tissues, they provide pivotal regulation of many biological processes. The present study defined miRNA expression during murine myogenic progenitor cell (MPC) proliferation and differentiation to identify miRNAs involved in muscle regeneration. Muscle-related gene expression analyses revealed that the time course and expression of myosin heavy chain (MHC) and transcription factors (Myf5, MyoD, myogenin, and Pax7) were similar during in vitro MPC proliferation/differentiation and in vivo muscle regeneration. Comprehensive profiling revealed that 139 or 16 miRNAs were significantly changed more than twofold [false discovery rate (FDR) < 0.05] during MPC differentiation or proliferation, respectively; cluster analyses revealed five distinct patterns of miRNA expression during the time course of MPC differentiation. Not unexpectedly, the largest miRNA changes occurred in muscle-specific miRNAs (miR-1, -133a, and -499), which were upregulated >10-fold during MPC differentiation (FDR < 0.01). However, several previously unreported miRNAs were differentially expressed, including miR-10b, -335-3p, and -682. Interestingly, the temporal patterns of miR-1, -499, and -682 expression during in vitro MPC proliferation/differentiation were remarkably similar to those observed during in vivo muscle regeneration. Moreover, in vitro inhibition of miR-682, the only miRNA upregulated in proliferating compared with quiescent MPC, led to decreased MPC proliferation, further validating our in vitro assay system for the identification of miRNAs involved in muscle regeneration. Thus the differentially expressed miRNAs identified in the present study could represent new regulatory elements in MPC proliferation and differentiation.

scholarly journals Effects of dietary supplementation of l-methionine vs. dl-methionine on performance, plasma concentrations of free amino acids and other metabolites, and myogenesis gene expression in young growing pigs

2018 ◽  
Vol 3 (1) ◽  
pp. 329-339 ◽  
Author(s):  
Zhongyue Yang ◽  
Md Shamimul Hasan ◽  
John K Htoo ◽  
Derris D Burnett ◽  
Jean M Feugang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Feed Intake ◽  
Myogenic Differentiation ◽  
Average Daily Gain ◽  
Plasma Concentrations ◽  
Growing Pigs ◽  
Feed Ratio ◽  
Nutrient Metabolism ◽  
Swine Industry ◽  
Myogenic Factors

Abstract Methionine (Met), the second or third limiting amino acid (AA) in typical swine diets, plays important roles in promoting swine health and growth, especially, muscle growth. Whereas dl-Met products have been used in swine industry for many years, l-Met products have been developed recently. This research was conducted to study the effects of supplemental l-Met or dl-Met on nutrient metabolism, muscle gene expression, and growth performance of pigs. Twenty crossbred young barrows (initial body weight [BW] 21.2 ± 2.7 kg) were randomly assigned to 20 individual pens and two dietary treatments according to a completely randomized design with pigs serving as the experiment unit (n = 10). Two corn and soybean meal-based diets (diets 1 and 2) were formulated to meet or exceed the recommended requirements for energy, AA, and other nutrients (NRC. 2012. Nutrient requirements of swine, 11th ed. Washington, DC: The National Academies Press; AMINODat 5.0). Crystalline l-Met and dl-Met were supplemented to diets 1 and 2 (both at 0.13%, as-fed basis), respectively. After 4 wk of an ad libitum feeding trial, BW and feed intake were measured to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F). Blood samples were collected from the jugular vein for analyses of plasma AA and metabolite concentrations. The longissimus dorsi muscle samples were collected for analysis of myogenesis gene expression. Data were analyzed using Student’s t-test. There were no differences (P = 0.56 to 0.94) in ADG, ADFI, or G:F between pigs fed the two experimental diets and no differences between diets were observed in plasma free AA concentrations. No differences were observed between pigs fed the two diets in expression of mRNA for eight myogenesis-related genes, which were myogenic differentiation 1, myogenin, myogenic factors 5, muscle regulatory factor 4 (a.k.a. myogenic factors 6), and myocyte enhancer factors 2A, 2B, 2C, and 2D. In conclusion, results of this experiment indicate that the bioefficacy of l-Met is not different from that of dl-Met, which is likely because of an efficient conversion of d-Met to l-Met by pigs.

Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3β

2007 ◽  
Vol 292 (5) ◽  
pp. C1636-C1644 ◽  
Author(s):  
Jos L. J. van der Velden ◽  
Ramon C. J. Langen ◽  
Marco C. J. M. Kelders ◽  
Jodil Willems ◽  
Emiel F. M. Wouters ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Glycogen Synthase ◽  
Myogenic Differentiation ◽  
Hindlimb Suspension ◽  
Akt Phosphorylation ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Myoblast Proliferation ◽  
Gsk 3Β ◽  
First Time

Muscle atrophy contributes to morbidity and mortality in aging and chronic disease, emphasizing the need to gain understanding of the mechanisms involved in muscle atrophy and (re)growth. We hypothesized that the magnitude of muscle regrowth during recovery from atrophy determines whether myonuclear accretion and myogenic differentiation are required and that insulin-like growth factor (IGF)-I/Akt/glycogen synthase kinase (GSK)-3β signaling differs between regrowth responses. To address this hypothesis we subjected mice to hindlimb suspension (HS) to induce atrophy of soleus (−40%) and plantaris (−27%) muscle. Reloading-induced muscle regrowth was complete after 14 days and involved an increase in IGF-IEa mRNA expression that coincided with Akt phosphorylation in both muscles. In contrast, phosphorylation and inactivation of GSK-3β were observed during soleus regrowth only. Furthermore, soleus but not plantaris regrowth involved muscle regeneration based on a transient increase in expression of histone 3.2 and myosin heavy chain-perinatal, which are markers of myoblast proliferation and differentiation, and a strong induction of muscle regulatory factor (MRF) expression. Experiments in cultured muscle cells showed that IGF-I-induced MRF expression is facilitated by inactivation of GSK-3β and selectively occurs in the myoblast population. This study suggests that induction of IGF-I expression and Akt phosphorylation during recovery from muscle atrophy is independent of the magnitude of muscle regrowth. Moreover, our data demonstrate for the first time that the regenerative response characterized by myoblast proliferation, differentiation, and increased MRF expression in recovering muscle is associated with the magnitude of regrowth and may be regulated by inactivation of GSK-3β.

Renal expression of IGF I in hypersomatotropic states

1990 ◽  
Vol 259 (2) ◽  
pp. F251-F257 ◽  
Author(s):  
S. B. Miller ◽  
P. Rotwein ◽  
J. D. Bortz ◽  
P. J. Bechtel ◽  
V. A. Hansen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pituitary Tumors ◽  
Tumor Bearing ◽  
Collecting Ducts ◽  
Igf I ◽  
Renal Size ◽  
Renal Expression ◽  
I Gene ◽  
Gh Excess ◽  
Stimulation Of

We examined insulin-like growth factor I (IGF I) gene expression in kidney in two models of hypersomatotropism, rats implanted with GH3 pituitary tumors, and rats administered exogenous growth hormone (GH). Both GH3 tumor-bearing rats and rats administered GH gained weight more rapidly than control animals, and had kidneys that were larger than those of controls. Tumor-bearing rats had increased levels of circulating IGF I. Glomeruli from tumor-implanted rats were sclerotic. Immunostainable IGF I was increased in medullary collecting ducts from tumor-bearing and GH-injected rats compared with kidneys from control animals. Levels of IGF I mRNA in kidneys of rats implanted with GH3 tumors and GH-injected rats were elevated compared with levels in kidneys from controls. Our findings demonstrate enhanced renal IGF I gene expression in hypersomatotropism. Stimulation of renal IGF I synthesis by GH could be causative of changes in renal function and renal size that occur in states of GH excess such as acromegaly.

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