ライフサイエンスコーパス: myostatin

1 fibers can be negatively regulated by bovine myostatin.

2 he heat shock response and the antagonism of myostatin.

3 olding and regulating biological activity of myostatin.

4 at has been identified in the serum bound to myostatin.

5 feration by antagonizing the TGF-beta ligand myostatin.

6 regions that harbor loci that interact with myostatin.

7 achexia by secreting peptide factors such as myostatin.

8 s accompanied by increased protein levels of myostatin.

9 is present extracellularly as uncleaved pro-myostatin.

10 signature, including increased expression of myostatin.

11 growth by altering the binding capacity for myostatin.

12 ng the interactions of GASP antagonists with myostatin.

13 ntibody LY2495655 (LY) binds and neutralises myostatin.

14 unique in that they specifically antagonize myostatin.

15 ets thyroid hormone-associated protein 1 and myostatin, 2 negative regulators of muscle growth and hy

16 Stroke injury acutely increased myostatin (3-fold) and lowered brain-derived neurotrophi

17 dependently of overexpression or knockout of myostatin, a key repressor of muscle development that ca

18 from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretio

19 We previously showed that expression of myostatin, a master negative regulator of skeletal muscl

20 Myostatin, a member of the TGF-beta family of ligands, i

21 Myostatin, a member of the TGF-beta super-family, is a p

22 To this end, we focused on blocking myostatin, a member of the transforming growth factor-be

23 Myostatin, a transforming growth factor-beta superfamily

24 and pig components, against the backdrop of myostatin, a universal sequence commonly found in mammal

25 Thus, the controlled inhibition of myostatin action could potentially help repair damaged c

26 least partially due to its ability to block myostatin, activin A, and transforming growth factor-bet

27 Here we show that myostatin/activin A inhibition can cause muscle hypertro

28 receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model o

29 Inhibition of myostatin/activin A signaling activated transcriptional

30 satellite cells playing little or no role in myostatin/activin A signaling in vivo and render support

31 ains in a competitive manner at the critical myostatin/activin binding site, hence preventing signal

32 New function of the myostatin/activin type I receptor (ALK4) as a mediator o

33 Interference with myostatin activity improves insulin sensitivity that was

34 statin interaction and significantly reduced myostatin activity upon L165041-mediated activation of P

35 hich functions through negatively modulating myostatin activity via a mechanism involving Gasp-1.

36 ses fiber area, consistent with reduction of myostatin activity.

37 Myostatin and activin A are structurally related secrete

38 The cellular targets for myostatin and activin A in muscle and the role of satell

39 , which encodes a high-affinity receptor for myostatin and activin A specifically in myofibers is suf

40 g or atrophying diseases, with a decrease of myostatin and activin receptor, and an increase of the m

41 ActRIIA in addition to ActRIIB in mediating myostatin and activin signaling and highlight the need f

42 action is likely due to its ability to block myostatin and enhance neovacularization.

43 Both myostatin and GDF11 affected synapse formation in isolat

44 Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and

45 MT attenuated the stroke-induced increase in myostatin and increased BDNF expression in skeletal musc

46 However, expression of myostatin and its cognate receptors in other tissues, in

47 We also show that both myostatin and its receptor were abundantly expressed in

48 In cultured cells, co-expression of pro-myostatin and latent transforming growth factor-beta-bin

49 ergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for t

50 Here, we aimed to decipher the role of myostatin and myostatin-dependent signaling pathways for

51 2/3, and thus presents a means of regulating myostatin and potentiating muscle growth.

52 Myostatin and the activins are capable of binding to bot

53 cuss the biochemical regulation of GDF11 and myostatin and their functions in the heart, skeletal mus

54 that multiple pathways, including decreased myostatin and up-regulated miRNAs, alpha-dystroglycan/li

55 ss development, including the ligands GDF-8 (myostatin) and GDF-11 (BMP-11).

56 WEAK/Fn14 axis; FOXO-1, Atrogin-1 and MuRF1; Myostatin) and increased anabolic intracellular pathways

57 markers and protein expression of PI3K/Akt, myostatin, and autophagy signaling were measured.

58 , it specifically induces IGF1 and represses myostatin, and expression of PGC-1alpha4 in vitro and in

59 Circulating insulin-like growth factor-1, myostatin, and growth and differentiation factor-15 were

60 f muscle mass--insulin-like growth factor-1, myostatin, and growth and differentiation factor-15--wer

61 Follistatin is a natural antagonist of myostatin, and over-expression of follistatin in mouse m

62 Myostatin antagonism might become a therapeutic strategy

63 e regulator of muscle regeneration, with the myostatin antagonist follistatin.

64 and activin receptor, and an increase of the myostatin antagonist, follistatin.

65 treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle m

66 sults in mice regarding the efficacy of anti-myostatin approaches and may inform patient selection an

67 y explain the poor clinical efficacy of anti-myostatin approaches in several of the clinical studies

68 al Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-sp

69 de support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-re

70 Finally, to investigate myostatin as a potential therapeutic target for the trea

71 domain (ND) of Fstl3 interacts uniquely with myostatin as compared with activin A, because it utilize

72 ecific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bb

73 Regulators of myostatin at the protein (AKT1) and miRNA (miR-539 and m

74 uous electropositive surface is created when myostatin binds Fst288, which significantly increases th

75 y favorable phenotype can be reproduced when myostatin blockade begins at an adult age.

76 ease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which n

77 uscle wasting in heart failure, we infused a myostatin blocking antibody (JA-16), which promoted grea

78 ed highly up-regulated expression of p21 and Myostatin, both inhibitors of myoblast proliferation.

79 ion solution structure of myostatin-free and myostatin-bound states of GASP-1 and GASP-2.

80 tatin, which increased circulating levels of myostatin by 3- to 4-fold, caused a reduction in weight

81 e signaling peptide requires cleavage of pro-myostatin by a proprotein convertase, which is thought t

82 n the extracellular matrix, and secreted pro-myostatin can be cleaved extracellularly by the proprote

83 or TGF-beta/activin family members including myostatin, can prevent or restore loss of lean body mass

84 orted to bind to and inhibit the activity of myostatin; consistent with this, we found that enhanced

85 e results demonstrate the mechanism by which Myostatin contributes to DNA damage in skeletal muscle o

86 Foxa2 transcriptionally up-regulated Myostatin, contributing to exaggerated oxidative stress

87 Parental myostatin deficiency (Mstn(tm1Sjl/+)) increases muscle m

88 In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial

89 This large rodent model of myostatin deficiency did not have the negative consequen

90 Myostatin deficiency has been well studied in mice, but

91 Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis

92 ts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantat

93 ent rats was markedly different from that of myostatin-deficient mice, which have impaired contractil

94 Overall, the muscle and tendon phenotype of myostatin-deficient rats was markedly different from tha

95 eractions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 o

96 aimed to decipher the role of myostatin and myostatin-dependent signaling pathways for cardiac funct

97 In support to this argument, we show that myostatin directly up-regulated lipogenic genes and incr

98 muscle growth that operates independently of myostatin-driven mechanisms.

99 y outstanding questions related to GDF11 and myostatin dynamics and signaling during development, gro

100 Skeletal muscle autophagic proteolysis and myostatin expression (inhibitor of protein synthesis) ar

101 the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity.

102 unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which s

103 ecific null mice, indicating that myocardial myostatin expression controls muscle atrophy in heart fa

104 e demonstrate that hyperammonemia stimulated myostatin expression in a NF-kappaB-dependent manner.

105 ith CKD, we found a 2- to 3-fold increase in myostatin expression in muscle.

106 hole-body muscle-to-fat ratio with increased myostatin expression in muscle.

107 duced muscle mass and strength and increased myostatin expression in wild-type compared with postdeve

108 monstrated a higher interleukin-15 and lower myostatin expression relative to controls, indicating a

109 n cultured muscle cells, TNF-alpha increased myostatin expression via a NF-kappaB-dependent pathway,

110 Myostatin expression was decreased in atrial appendages

111 iation with Bbaa1 arthritis development, and myostatin expression was linked to IFN-beta production.

112 Additionally, myostatin expression was upregulated in Smad7(-/-) muscl

113 The BCAA/LEU supplement did not alter myostatin expression, but mTOR signaling, autophagy meas

114 al muscle molecular markers showed increased myostatin expression, impaired mTOR signaling, and incre

115 conditions, expression of DN FoxO decreased myostatin expression, increased MyoD expression and sate

116 The increased skeletal muscle myostatin expression, reduced mammalian target of rapamy

117 ression of Numb in satellite cells inhibited Myostatin expression.

118 intaining Akt phosphorylation and inhibiting myostatin expression.C

119 lation of growth-inhibitory genes, including myostatin, Fbxo32 (MAFbx), and Trim63 (MuRF1).

120 e First low resolution solution structure of myostatin-free and myostatin-bound states of GASP-1 and

121 more tight binding with the mature peptide, myostatin function is inhibited, resulting in the change

122 The TGF-beta family ligands myostatin, GDF11, and activins are negative regulators o

123 mpared with other TGFbeta superfamily member myostatin (GDF8).

124 n with a naturally occurring mutation in the myostatin gene (Compact (Cmpt)) leading to a hypermuscul

125 ency of the C-variant (g.66493737C/T) at the myostatin gene (MSTN) in cohorts of the Thoroughbred hor

126 The first two exons of myostatin gene code for the N-propeptide and its third e

127 Myostatin gene inactivation prevented the severe loss of

128 a variation in the 5' flanking region of the myostatin gene is associated with the genetic regulation

129 n the myostatin promoter, and stimulation of myostatin gene transcription.

130 in % (w/w), a reference system based on the myostatin gene was used.

131 nt study, the coding region of bMSTN (bovine myostatin) gene was amplified and mutated (A224C and G93

132 Previously, we found that Myostatin genotype, reciprocal cross, and sex interacted

133 A total of 12 of these QTL interacted with myostatin genotype.

134 n activating growth factors, such as BMP2/4, myostatin, growth differentiation factor 11, and transfo

135 tors of muscle mass (e.g., MAFbx, MURF1, and myostatin) had peaked on days 2-4 but normalized by day

136 egeneration, primarily through inhibition of myostatin, have shown promise in the laboratory and are

137 ore potent than GASP-2, preferentially binds myostatin in an asymmetrical 1:1 complex, whereas GASP-2

138 Targeted inhibition of myostatin in cardiac cachexia might be a therapeutic opt

139 n dose-dependently inhibited the response to myostatin in cardiomyocytes and in perfused mouse hearts

140 glycogen accumulation after inactivation of myostatin in cardiomyocytes.

141 Here, we present the crystal structure of myostatin in complex with Fstl3.

142 Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288

143 respect to a potential role for GDF11 and/or myostatin in humans with heart disease.

144 ta-binding protein-3 (LTBP-3) sequesters pro-myostatin in the extracellular matrix, and secreted pro-

145 Our results uncover an important role of myostatin in the heart for maintaining cardiac energy ho

146 However, the function of myostatin in the heart is barely understood, although it

147 er, our results reveal an essential role for myostatin in the pathogenesis of cancer cachexia and lin

148 ls, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to

149 Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduc

150 ants, we generated a mouse model that allows myostatin inactivation in adult cardiomyocytes.

151 achexia, combined inhibition of activins and myostatin increased mass or prevented muscle wasting, re

152 Inhibiting myostatin induced a more profound increase in muscle mas

153 Loss of myostatin induced eccentric hypertrophy and enhanced car

154 Myostatin induced phosphorylation of Smad3 in hMSCs; kno

155 The conclusion is that myostatin inhibited adipogenesis in human bone marrow-de

156 Pharmacological myostatin inhibition also decreased the rate of protein

157 Here, we show that myostatin inhibition by follistatin transgene expression

158 ng efficacies, depending on the age at which myostatin inhibition occurs.

159 We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal

160 Various myostatin inhibitor approaches have been identified and

161 tegies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal admi

162 ficacy of both SMN2 splicing modifiers and a myostatin inhibitor in mice at later disease stages.

163 Myostatin inhibitors are currently being pursued as ther

164 Further evaluation of more potent myostatin inhibitors for stimulating muscle growth in mu

165 New advances in the use of potent myostatin inhibitors have made this an attractive approa

166 Remarkably, codelivery of activin and myostatin inhibitors induced a synergistic response, res

167 e hypothesis that systemic administration of myostatin inhibitors provides an adequate safety margin

168 will be paramount to the rational design of myostatin inhibitors that could be used in the treatment

169 truncations of GASP-1 result in less potent myostatin inhibitors that form a 2:1 complex, suggesting

170 s field to include more novel agents such as myostatin inhibitors.

171 Myostatin inhibits skeletal muscle growth.

172 hanced secretion of Gasp-1, increased Gasp-1 myostatin interaction and significantly reduced myostati

173 owever, in contrast, the prodomain of GDF-8 (myostatin) interacts with the glycosaminoglycan side cha

174 liferation of muscle fibroblasts, induced by myostatin, involves the activation of Smad, p38 MAPK and

175 Myostatin is a cytokine of the transforming growth facto

176 Myostatin is a major negative regulator of skeletal musc

177 Myostatin is a member of the transforming growth factor-

178 Myostatin is a muscle-specific member of the TGF-beta su

179 Myostatin is a negative regulator of muscle mass.

180 Myostatin is a negative regulator of skeletal muscle and

181 sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target.

182 Our studies support the novel concept that myostatin is a repressor of physiological cardiac muscle

183 Myostatin is a secreted signaling molecule that normally

184 For instance, the TGF-beta ligand myostatin is a staunch negative regulator of muscle grow

185 Myostatin is a transforming growth factor-beta family me

186 regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of post

187 Myostatin is an endogenous negative regulator of muscle

188 ested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of c

189 Similar to other TGF-beta family ligands, myostatin is neutralized by binding one of a number of s

190 find that in skeletal muscle, unlike serum, myostatin is present extracellularly as uncleaved pro-my

191 Myostatin is secreted as a latent configuration formed b

192 Myostatin is tightly controlled by Fst-like 3 (Fstl3), w

193 GDF8, or myostatin, is a member of the TGF-beta superfamily of se

194 in wild-type compared with postdevelopmental myostatin knockout mice.

195 nsulin-like growth factor-1 and unexpectedly myostatin, known mediators of muscle hypertrophy and atr

196 Indeed, myostatin levels in the plasma were significantly increa

197 Notably, myostatin loss also impeded the growth of LLC tumors, th

198 Mechanistically, myostatin loss attenuated the activation of muscle fiber

199 Muscle expression of myostatin, mammalian target of rapamycin (mTOR) targets,

200 Myostatin may be a useful target for drug development fo

201 her these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in

202 In Myostatin(-/-) mice however, Streptozotocin treatment di

203 Moreover, Foxa2 levels remained unaltered in Myostatin(-/-) mice, while levels of p63/REDD1 were high

204 nd 8.5-fold (P < 0.001) higher expression of myostatin mRNA and protein in patients.

205 1) and miRNA (miR-539 and miR-208b targeting myostatin mRNA) levels were altered in GRMD CS, consiste

206 We used a Cre/loxP system to ablate myostatin (Mstn gene) expression in a cell type-specific

207 ucleases were used to genetically inactivate myostatin (MSTN(Delta/Delta) ) would exhibit an increase

208 Muscle growth is negatively regulated by myostatin (MSTN) and activins.

209 Myostatin (MSTN) and growth and differentiation factor-1

210 Null mutations of myostatin (Mstn) are associated with increased muscle ma

211 Myostatin (MSTN) belongs to the transforming growth fact

212 ac as well as skeletal muscle cells promotes myostatin (Mstn) expression.

213 The myostatin (MSTN) gene is important because of its role i

214 High doses of dexamethasone (Dex) or myostatin (Mstn) induce severe atrophy of skeletal muscl

215 Myostatin (Mstn) is a conserved negative regulator of sk

216 Myostatin (MSTN) is a dominant inhibitor of skeletal mus

217 Myostatin (MSTN) is a member of the transforming growth

218 Myostatin (MSTN) is a negative regulator of skeletal mus

219 Myostatin (Mstn) is predominantly expressed in skeletal

220 The growth factor myostatin (MSTN) negatively regulates skeletal muscle gr

221 Ablating myostatin (Mstn) prevents obesity, so we investigated if

222 ntagonist of another TGF-beta family member, myostatin (Mstn), for the promotion of muscle growth in

223 gen-related receptor gamma (Errgamma) on the myostatin (Mtn) mouse null background (Mtn(-/-)/Errgamma

224 NA damage and muscle atrophy was observed in Myostatin(-/-) muscle in response to Streptozotocin trea

225 ccurring in constitutive and germ-line-based myostatin mutants, we generated a mouse model that allow

226 A non-functional myostatin mutation leads to a double muscling phenotype

227 a safety trial of a neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becke

228 Although myostatin negatively regulates skeletal muscle growth, i

229 We now demonstrate that myostatin not only regulates the growth of myocytes but

230 output and beta-adrenergic responsiveness of myostatin null mice was therefore due to increased SR Ca

231 This was due to myostatin null ventricular myocytes having larger [Ca(2+

232 F2 population of 1000 mice derived from the Myostatin-null C57BL/6 and M16i mouse lines, six imprint

233 were collected on F2 progeny derived from a myostatin-null C57BL/6 strain by M16i cross.

234 atellite cell loss also persists with age in myostatin-null mice regardless of increased muscle mass.

235 o and liver regeneration via the analysis of myostatin-null mice, in which skeletal muscle is hypertr

236 tegrin-linked kinase are dysregulated in the myostatin-null mice.

237 5 inhibitor blocked the inhibitory effect of myostatin on adipogenesis in hMSCs, implying an importan

238 The effects of myostatin on adipogenic differentiation are poorly under

239 needed to determine whether direct impact of myostatin on liver and aortic endothelium may contribute

240 ieves only a partial signaling blockade upon myostatin or activin A stimulation, and this leads to on

241 Genetic disruption of myostatin or its related signaling is known to cause str

242 Myostatin (or GDF8) and GDF11 are potent negative regula

243 Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the t

244 Myostatin, or GDF8, is an inhibitor of skeletal muscle g

245 effects of the age-dependent decline of the myostatin paralog growth and differentiation factor 11.

246 arin coding gene Mtm1) that a down-regulated myostatin pathway can be reactivated by correcting the u

247 Several drugs targeting the myostatin pathway have been used in clinical trials to i

248 lity, we examined the effect of blocking the myostatin pathway in dysferlin-deficient (Dysf(-/-)) mic

249 Use of a soluble ActRIIB-Fc "trap," to block myostatin pathway signaling in normal or cachectic mice

250 myonuclear degeneration and the role of the myostatin pathway.

251 ional environment, and specifically prenatal myostatin pathways, provides a potential therapeutic win

252 bition by subcutaneous injections of an anti-myostatin peptibody into CKD mice (IC(50) approximately

253 cle (n = 15) and MCAO mice receiving an anti-myostatin PINTA745 (n = 12; subcutaneous injection of 7.

254 AAV-mediated expression of myostatin pro-peptide D76A mutant in adult Ldlr null mic

255 we reported that AAV-mediated delivery of a myostatin pro-peptide D76A mutant in adult mice attenuat

256 ull mice resulted in sustained expression of myostatin pro-peptide in the liver.

257 paB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene tr

258 determined the effects of human recombinant myostatin protein on adipogenesis of bone marrow-derived

259 pQTL, tQTL and eQTL that interacted with Myostatin, reciprocal cross, and sex were detected as we

260 Co-expression of LTBP-3 with myostatin reduces phosphorylation of Smad2, and ectopic

261 ce of the endogenous muscle growth regulator myostatin, regeneration of muscle is enhanced, and muscl

262 mice, but limited data are available on how myostatin regulates the structure and function of muscle

263 for the first time show the role of Foxa2 in Myostatin regulation in skeletal muscle in diabetic mice

264 Myostatin released from cardiomyocytes induces skeletal

265 We found that myostatin represses AMP-activated kinase activation in t

266 re identified to significantly interact with myostatin, sex or reciprocal cross.

267 Myostatin showed an age-dependent decrease and an invers

268 An analysis of a Tcap binding protein, myostatin, showed that deletion of Tcap was accompanied

269 Modalities that inhibit myostatin signaling are currently in clinical trials for

270 study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/

271 ac MRI revealed that genetic inactivation of myostatin signaling in the adult murine heart caused car

272 Loss or blockade of myostatin signaling increases muscle mass and improves m

273 Inhibition of myostatin signaling increases muscle mass, and therapeut

274 how that the expression of components of the myostatin signaling pathway is downregulated in muscle w

275 IIB receptor (ActRIIB)-mFc (an inhibitor of myostatin signaling) to promote hypertrophy and increase

276 GRMD CS, consistent with down-regulation of myostatin signaling, CS hypertrophy, and functional resc

277 Smad7 inhibits intracellular myostatin signalling via Smad2/3, and thus presents a me

278 Myostatin significantly down-regulated the expression of

279 In this study, we used myostatin small interfering (si)RNA (siGDF-8), a major i

280 Transfection with Myostatin-specific siRNA rescued the proliferation defec

281 Furthermore, myostatin stimulated expression of regulator of G-protei

282 ent pathway, whereas muscle cells exposed to myostatin stimulated IL-6 production via p38 MAPK and ME

283 Our results show that myostatin stimulates the proliferation of muscle fibrobl

284 Therefore, an anti-myostatin strategy can improve skeletal muscle recovery

285 eEF2, ERK1/2 and UBF; gene expression of the myostatin target Mighty as well as c-Myc and its targets

286 associated with higher muscle expression of myostatin than placebo.

287 identified several characteristics unique to myostatin that will be paramount to the rational design

288 h factor-beta superfamily members, including myostatin, that are involved in the negative regulation

289 in breakdown, we conclude that CKD increases myostatin through cytokine-activated pathways, leading t

290 re are loci in the genome that interact with myostatin to control backfat depth and other complex tra

291 designed to identify loci that interact with myostatin to impact growth traits in mice.

292 ted at developing drugs capable of targeting myostatin to treat patients with muscle loss.

293 ion or gene silencing of NF-kappaB abolished myostatin up-regulation under conditions of hyperammonem

294 In addition, inhibiting myostatin using intramuscular injection of AAV1-follista

295 We find that the prehelix region of myostatin very closely resembles that of TGF-beta class

296 Local inhibition of myostatin was also not affected by rapamycin and may con

297 ed medium (CM), but IL-6, OSM, TNFalpha, and myostatin were not.

298 Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated c

299 Moreover, cardiac-specific overexpression of myostatin, which increased circulating levels of myostat

300 ltured aortic endothelial cells responded to myostatin with a reduction in eNOS phosphorylation and a