Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

1997 ◽  
Vol 83 (4) ◽  
pp. 1270-1275 ◽  
Author(s):  
Daniel R. Marsh ◽  
David S. Criswell ◽  
James A. Carson ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Young Adult ◽  
Muscle Regeneration ◽  
Tibialis Anterior Muscle ◽  
Brown Norway ◽  
Mrna Levels ◽  
Myogenic Regulatory Factors ◽  
Adult Rats ◽  
Regulatory Factors ◽  
Old Rats

Marsh, Daniel R., David S. Criswell, James A. Carson, and Frank W. Booth. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270–1275, 1997.—Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

Expression of acetylcholine receptor mRNAs in atrophying and nonatrophying skeletal muscles of old rats

1998 ◽  
Vol 85 (5) ◽  
pp. 1903-1908 ◽  
Author(s):  
Ronald R. Gomes ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Acetylcholine Receptor ◽  
Biceps Brachii ◽  
Male Rats ◽  
Brown Norway ◽  
Mrna Levels ◽  
Adult Rats ◽  
Γ Subunit ◽  
Age Related ◽  
Old Rats

We examined the age-related association in skeletal muscle between atrophy and expression of mRNAs encoding both the γ-subunit of the nicotinic acetylcholine receptor (AChR), and myogenin, a transcription factor that upregulates expression of the γ-subunit promoter. Gastrocnemius and biceps brachii muscles were collected from young (2-mo-old), adult (18-mo-old), and old (31-mo-old) Fischer 344/Brown Norway F1 generation cross male rats. In the gastrocnemius muscles of old vs. young and adult rats, lower muscle mass was accompanied by significantly elevated AChR γ-subunit and myogenin mRNA levels. In contrast, the biceps brachii muscle exhibited neither atrophy nor as drastic a change in AChR γ-subunit and myogenin mRNA levels with age. Expression of the AChR ε-subunit mRNA did not change with age in either gastrocnemius or biceps brachii muscles. Thus changes in skeletal muscle AChR γ-subunit and myogenin mRNA levels may be more related to atrophy than to chronological age in old rats.

scholarly journals Differential effects of targeted tongue exercise and treadmill running on aging tongue muscle structure and contractile properties

2013 ◽  
Vol 114 (4) ◽  
pp. 472-481 ◽  
Author(s):  
Heidi Kletzien ◽  
John A. Russell ◽  
Glen E. Leverson ◽  
Nadine P. Connor
Keyword(s):  
Young Adult ◽  
Exercise Group ◽  
Contractile Properties ◽  
Treadmill Running ◽  
Brown Norway ◽  
Middle Aged ◽  
Adult Rats ◽  
Tongue Muscle ◽  
Muscle Structure ◽  
Old Rats

Age-associated changes in tongue muscle structure and strength may contribute to dysphagia in elderly people. Tongue exercise is a current treatment option. We hypothesized that targeted tongue exercise and nontargeted exercise that activates tongue muscles as a consequence of increased respiratory drive, such as treadmill running, are associated with different patterns of tongue muscle contraction and genioglossus (GG) muscle biochemistry. Thirty-one young adult, 34 middle-aged, and 37 old Fischer 344/Brown Norway rats received either targeted tongue exercise, treadmill running, or no exercise (5 days/wk for 8 wk). Protrusive tongue muscle contractile properties and myosin heavy chain (MHC) composition in the GG were examined at the end of 8 wk across groups. Significant age effects were found for maximal twitch and tetanic tension (greatest in young adult rats), MHCIIb (highest proportion in young adult rats), MHCIIx (highest proportion in middle-aged and old rats), and MHCI (highest proportion in old rats). The targeted tongue exercise group had the greatest maximal twitch tension and the highest proportion of MHCI. The treadmill running group had the shortest half-decay time, the lowest proportion of MHCIIa, and the highest proportion of MHCIIb. Fatigue was significantly less in the young adult treadmill running group and the old targeted tongue exercise group than in other groups. Thus, tongue muscle structure and contractile properties were affected by both targeted tongue exercise and treadmill running, but in different ways. Studies geared toward optimizing dose and manner of providing targeted and generalized tongue exercise may lead to alternative tongue exercise delivery strategies.

Myogenic regulatory factors transactivate the Tceal7 gene and modulate muscle differentiation

2010 ◽  
Vol 428 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Xiaozhong Shi ◽  
Daniel J. Garry
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Development ◽  
Cellular Proliferation ◽  
Elongation Factor ◽  
Muscle Differentiation ◽  
Myogenic Regulatory Factors ◽  
Mobility Shift ◽  
Regulatory Factors ◽  
E Box

Recurrent injuries eventually exhaust the capacity of skeletal muscle to fully restore or regenerate its cellular architecture. Therefore a comprehensive understanding of the muscle regeneration programme is needed to provide a platform for new therapies for devastating diseases such as Duchenne muscular dystrophy. To begin to decipher the molecular programme that directs muscle regeneration, we undertook an unbiased strategy using microarray analysis of cardiotoxin-injured skeletal muscle at defined time periods in the adult mouse. Using this strategy, we identified Tceal7 [transcription elongation factor A (SII)-like 7], which was dynamically regulated during muscle regeneration. Our studies revealed that Tceal7 was restricted to the skeletal muscle lineage during embryogenesis. Using transgenic technologies and transcriptional assays, we defined an upstream 0.7 kb fragment of the Tceal7 gene that directed the LacZ reporter to the developing skeletal muscle lineage. Analysis of the Tceal7 promoter revealed evolutionarily conserved E-box motifs within the 0.7 kb upstream fragment that were essential for promoter activity, as mutation of the E-box motifs resulted in the loss of reporter expression in the somites of transgenic embryos. Furthermore, we demonstrated that MRFs (myogenic regulatory factors) were Tceal7 upstream transactivators using transcriptional assays, EMSAs (electrophoretic mobility-shift assays), and ChIP (chromatin immunoprecipitation) assays. Overexpression of Tceal7 in C2C12 myoblasts decreased cellular proliferation and enhanced differentiation. Further studies revealed that p27 expression was up-regulated following Tceal7 overexpression. These studies support the hypothesis that MRFs transactivate Tceal7 gene expression and promote muscle differentiation during muscle development and regeneration.

scholarly journals OR-009 The expression and roles of lncRNAs in the regeneration of skeletal muscle contusion

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Lifang Zheng ◽  
Peijie Chen ◽  
Weihua Xiao
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Control Group ◽  
Myogenic Regulatory Factors ◽  
Post Injury ◽  
Regulatory Factors ◽  
Expression Levels ◽  
Skeletal Muscle Contusion

Objective In recent years, Accumulating evidence from myoblast differentiation in vitro, cardiotoxin (CTX)-mediated injury or mdx mice suggested that some lncRNAs such as Malat1, H19, linc-MD1, linc-YY1, Sirt1 AS and lnc-mg may modulate myogenesis and muscle regeneration. However, the change of lncRNAs in skeletal muscle contusion and their possible roles are still unclear. We hypothesize that the lncRNAs may be involved in the repair of skeletal muscle contusion. Methods Forty C57BL/6 male mice were randomly divided into two groups, uninjured control group (group C) and muscle contusion group (group S). The mice of group S suffered from contusion injury. All the mice were killed to harvest gastrocnemius at 3, 6, 12 and 24 days post-injury. The gene expression were detected by PCR technique. Gastrocnemius were stained with H & E to evaluate the general morphology. Data were analyzed by One-way analysis of variance, with statistical significance being set at p ≤ 0.05. Results The expression levels of linc-MD1 and Sirt1 AS were significantly higher than that of the uninjured control group at 3, 6 and 12 days post-injury (p<0.01). And Malat1 was highly expressed in the skeletal muscle of the muscle contusion group at 3 days post-injury and continuously up-regulated at 6 days (p<0.01). Moreover, linc-YY1 and H19 were all elevated significantly at 6 days (all p<0.01), but their gene expression levels did not change significantly at 3, 12 and 24 days post-injury, as compared to the uninjured control group. Furthermore, lnc-mg mRNA level did not change significantly in the whole process of regeneration after muscle contusion except the time point of 12 days post-injury which decreased significantly (p<0.01). The expression of myogenic regulatory factors (MyoD, myogenin, myf5, myf6) were studied, they were all elevated significantly at 3 and 6 days (all p<0.01; except myogenin ), and returned to normal at 24 days post-injury, as compared to the uninjured control group. Meanwhile, Pearson correlations showed that there was an correlation between lincRNAs and myogenic regulatory factors mentioned above. Conclusions The expression of myogenic regulatory factors increased significantly after muscle contusion. Meanwhile, varieties of lncRNAs (Malat1, H19, lnc-mg, linc-MD1, linc-YY1, Sirt1 AS) were also up-regulated. Moreover, there was correlation between lncRNAs and myogenic regulatory factors for skeletal muscle regeneration. These results suggest that lncRNAs may play important roles in the regeneration of skeletal muscle contusion.

scholarly journals Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats

2002 ◽  
Vol 282 (2) ◽  
pp. R411-R422 ◽  
Author(s):  
Stephen E. Alway ◽  
Hans Degens ◽  
Dawn A. Lowe ◽  
Gururaj Krishnamurthy
Keyword(s):  
Young Adult ◽  
Mrna Level ◽  
Brown Norway ◽  
Mrna Levels ◽  
Aged Rats ◽  
Adult Rats ◽  
Protein Levels ◽  
Fast And Slow Muscles ◽  
Hindlimb Muscles ◽  
Gastrocnemius Muscles

The objective of this study was to determine if levels of repressors to myogenic regulatory factors (MRFs) differ between muscles from young adult and aged animals. Total RNA from plantaris, gastrocnemius, and soleus muscles of Fischer 344 × Brown Norway rats aged 9 mo (young adult, n = 10) and 37 mo (aged, n = 10) was reverse transcribed and then amplified by PCR. To obtain a semiquantitative measure of the mRNA levels, PCR signals were normalized to cyclophilin or 18S signals from the corresponding reverse transcription product. Normalization to cyclophilin and 18S gave similar results. The mRNA levels of MyoD and myogenin were ∼275–650% ( P < 0.001) and ∼500–1,100% ( P < 0.001) greater, respectively, in muscles from aged compared with young adults. In contrast, the protein levels were lower in plantaris and gastrocnemius muscles and similar in the soleus muscle of aged vs. young adult rats. Id repressor mRNA levels were ∼300–900% greater in fast and slow muscles of aged animals ( P ≤ 0.02), and Mist 1 mRNA was ∼50% greater in the plantaris and gastrocnemius muscles ( P< 0.01). The mRNA level of Twist mRNA was not significantly affected by aging. Id-1, Id-2, and Id-3 protein levels were ∼17–740% greater ( P < 0.05) in hindlimb muscles of aged rats compared with young adult rats. The elevated levels of Id mRNA and protein suggest that MRF repressors may play a role in gene regulation of fast and slow muscles in aged rats.

Association of insulin-like growth factor mRNA expressions with muscle regeneration in young, adult, and old rats

1997 ◽  
Vol 273 (1) ◽  
pp. R353-R358 ◽  
Author(s):  
D. R. Marsh ◽  
D. S. Criswell ◽  
M. T. Hamilton ◽  
F. W. Booth
Keyword(s):  
Young Adult ◽  
Growth Factor ◽  
Mrna Expression ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Insulin Like Growth Factor ◽  
Adult Rats ◽  
Young Rats ◽  
Igf I ◽  
Old Rats

The purpose of this study was to determine whether impaired regeneration of skeletal muscle in old rats can be attributed to diminished expression of insulin-like growth factor (IGF) mRNAs. Fischer 344 male rats aged 2 (young), 12 (adult), and 24 mo (old) were given an injection of the myotoxic anesthetic, bupivacaine, into the left tibialis anterior muscle. Muscle mass and protein concentration recovered to contralateral control values by 28 days in young, but not adult or old rats. The temporal and maximal expressions of IGF-I mRNA were similar during recovery from bupivacaine on days 5 and 10 in young, adult, and old rat muscles. IGF-I mRNA levels were reduced toward control levels in young rats by 15 days, but remained elevated in adult and old rats. IGF-I receptor mRNA in bupivacaine-injected muscle of old rats was elevated significantly higher than injected muscle of young and adult rats at recovery day 5. Five days after bupivacaine injection, IGF-II mRNA was increased 46-fold in young rats but was only increased fourfold in adult rats. Thereafter, IGF-II mRNA expression was similar for young, adult, and old rats at 10 and 15 days of recovery. In summary, we demonstrate that impaired regeneration of the tibialis anterior muscle in adult or old rats after bupivacaine-induced damage is associated with a prolonged elevation of IGF-I mRNA expression and/or diminished initial IGF-II mRNA expression.

scholarly journals Stimulus-specific adaptation in auditory thalamus of young and aged awake rats

2013 ◽  
Vol 110 (8) ◽  
pp. 1892-1902 ◽  
Author(s):  
Ben D. Richardson ◽  
Kenneth E. Hancock ◽  
Donald M. Caspary
Keyword(s):  
Young Adult ◽  
Auditory Cortex ◽  
Brown Norway ◽  
Oddball Paradigm ◽  
Adult Rats ◽  
Specific Adaptation ◽  
Auditory Thalamus ◽  
Gating Mechanism ◽  
Medial Geniculate ◽  
Awake Rats

Novel stimulus detection by single neurons in the auditory system, known as stimulus-specific adaptation (SSA), appears to function as a real-time filtering/gating mechanism in processing acoustic information. Particular stimulus paradigms allowing for quantification of a neuron's ability to detect novel or deviant stimuli have been used to examine SSA in the inferior colliculus, medial geniculate body (MGB), and auditory cortex of anesthetized rodents. However, the study of SSA in awake animals is limited to auditory cortex. The present study used individually advanceable tetrodes to record single-unit responses from auditory thalamus (MGB) of awake young adult and aged Fischer Brown Norway (FBN) rats to 1) examine the presence of SSA in the MGB of awake rats and 2) determine whether SSA is altered by aging in MGB. MGB single units in awake FBN rats displayed SSA in response to two stimulus paradigms: the oddball paradigm and a random blocked/interleaved presentation of a set of frequencies. SSA levels were modestly, but nonsignificantly, increased in the nonlemniscal regions of the MGB and at lower stimulus intensities, where 27 of 57 (47%) young adult MGB units displayed SSA. The present findings provide the initial description of SSA in the MGB of awake rats and support SSA as being qualitatively independent of arousal level or anesthetized state. Finally, contrary to previous studies in auditory cortex of anesthetized rats, MGB units in aged rats showed SSA levels indistinguishable from SSA levels in young adult rats, suggesting that SSA in MGB was not impacted by aging in an awake preparation.

Glutamine synthetase induction by glucocorticoids is preserved in skeletal muscle of aged rats

1996 ◽  
Vol 271 (6) ◽  
pp. E1061-E1066 ◽  
Author(s):  
D. Meynial-Denis ◽  
M. Mignon ◽  
A. Miri ◽  
J. Imbert ◽  
E. Aurousseau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glutamine Synthetase ◽  
Skeletal Muscles ◽  
Female Rats ◽  
Mrna Levels ◽  
Aged Rats ◽  
Adult Rats ◽  
Adult Age ◽  
Slow Twitch ◽  
Fast Twitch

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

Increased NHE2 expression in rat intestinal epithelium during ontogeny is transcriptionally mediated

1998 ◽  
Vol 275 (4) ◽  
pp. C1143-C1150 ◽  
Author(s):  
James F. Collins ◽  
Pawel R. Kiela ◽  
Hua Xu ◽  
Jiamin Zeng ◽  
Fayez K. Ghishan
Keyword(s):  
Northern Blot ◽  
Membrane Vesicle ◽  
Mrna Levels ◽  
Rat Intestine ◽  
Functional Protein ◽  
Adult Rats ◽  
Specific Staining ◽  
Western Blots ◽  
Intestinal Membrane ◽  
Old Rats

We have previously described changes in intestinal brush-border membrane vesicle (BBMV) Na+/H+exchange activity and characterized Na+/H+exchanger (NHE3) expression during rat ontogeny. The current studies were designed to investigate developmental changes in NHE2 expression in rat intestine. In previous studies, pH-dependent uptake of Na+ in jejunal BBMV utilizing HOE-694 inhibition demonstrated that NHE2 functional protein levels were lowest in 2-wk-old rats, higher in 3-wk-old and adult rats, and highest in 6-wk-old rats [Collins et al. Am. J. Physiol. 273 ( Cell Physiol. 42): C1937–C1946, 1997]. In the current investigation, Northern blot analyses showed that NHE2 mRNA levels in the jejunum were similar in 6-wk-old, adult, and 3-wk-old rats and three- to fivefold lower in 2-wk-old rats. In situ hybridization of 2- and 6-wk-old rat intestine with NHE2-specific probes confirmed Northern blot observations. Polyclonal antibodies were developed against an NHE2-specific peptide from amino acids 652–661. Western blots with NHE2 antiserum showed that the intensity of a specific 90-kDa band was lowest in 2-wk-old animals and four- to sixfold higher in 3- and 6-wk-old and adult animals. Immunohistochemical analysis showed specific staining of NHE2 antiserum to only the apical intestinal membrane. Furthermore, nuclear run-on analyses showed a 1.7-fold higher NHE2 transcription rate in 6-wk-old rats than in 2-wk-old rats. Overall, the current data suggest that increases in NHE2 expression upon weaning are mediated by increased gene transcription.

scholarly journals Conditional Deletion of Dicer in Adult Mice Impairs Skeletal Muscle Regeneration

2019 ◽  
Vol 20 (22) ◽  
pp. 5686 ◽  
Author(s):  
Satoshi Oikawa ◽  
Minjung Lee ◽  
Takayuki Akimoto
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Tibialis Anterior Muscle ◽  
Critical Factor ◽  
Skeletal Muscle Regeneration ◽  
Small Noncoding Rnas ◽  
Adult Mice

Skeletal muscle has a remarkable regenerative capacity, which is orchestrated by multiple processes, including the proliferation, fusion, and differentiation of the resident stem cells in muscle. MicroRNAs (miRNAs) are small noncoding RNAs that mediate the translational repression or degradation of mRNA to regulate diverse biological functions. Previous studies have suggested that several miRNAs play important roles in myoblast proliferation and differentiation in vitro. However, their potential roles in skeletal muscle regeneration in vivo have not been fully established. In this study, we generated a mouse in which the Dicer gene, which encodes an enzyme essential in miRNA processing, was knocked out in a tamoxifen-inducible way (iDicer KO mouse) and determined its regenerative potential after cardiotoxin-induced acute muscle injury. Dicer mRNA expression was significantly reduced in the tibialis anterior muscle of the iDicer KO mice, whereas the expression of muscle-enriched miRNAs was only slightly reduced in the Dicer-deficient muscles. After cardiotoxin injection, the iDicer KO mice showed impaired muscle regeneration. We also demonstrated that the number of PAX7+ cells, cell proliferation, and the myogenic differentiation capacity of the primary myoblasts did not differ between the wild-type and the iDicer KO mice. Taken together, these data demonstrate that Dicer is a critical factor for muscle regeneration in vivo.

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