Myostatin基因突变激发骨骼肌发育机制研究进展

doi:10.19586/j.2095-2341.2021.0053

生物技术进展 ›› 2021, Vol. 11 ›› Issue (4): 476-482.DOI: 10.19586/j.2095-2341.2021.0053

Myostatin基因突变激发骨骼肌发育机制研究进展

高丽¹(), 杨磊², 李光鹏²()

^1.包头师范学院生物科学与技术学院，内蒙古包头 014030
^2.内蒙古大学生命科学学院，省部共建草原家畜生殖调控与繁育国家重点实验室，呼和浩特 010030

收稿日期:2021-04-19 接受日期:2021-06-07 出版日期:2021-07-25 发布日期:2021-08-02
通讯作者: 李光鹏
作者简介:高丽 E-mail: gaoli8905@163.com；
基金资助:
内蒙古自治区科技重大专项项目(2020ZD0008);包头市青年创新人才项目(2010)

Research Progress on the Mechanism of Skeletal Muscle Development Stimulated by Myostatin Gene Mutation

Li GAO¹(), Lei YANG², Guangpeng LI²()

^1.School of Biology Science and Technology，Baotou Teacher’s College，Inner Mongolia Baotou 014030，China
^2.State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock，College of Life Sciences，Inner Mongolia University，Hohhot 010030，China

Received:2021-04-19 Accepted:2021-06-07 Online:2021-07-25 Published:2021-08-02
Contact: Guangpeng LI

摘要/Abstract

摘要：

肌肉生长抑制素基因（myostatin，MSTN）是骨骼肌发育的负调节因子，在不同物种中具有高度保守性。自然突变或通过基因编辑技术对该基因进行操作，均可以获得肌肉异常发达的动物个体。研究表明，MSTN基因突变可以通过多种调控途径影响肌肉发育过程。因此，从成肌细胞增殖、分化、蛋白质合成分解代谢、组蛋白修饰以及巨噬细胞极化等5个方面对MSTN突变促进肌肉发育的机理进行综述，以期为农业动物育种新材料生产及重大恶病质的治疗提供借鉴。

关键词: 基因突变, 细胞增殖, 蛋白质合成, 组蛋白修饰, 巨噬细胞极化

Abstract:

Myostatin （MSTN） is a negative regulator of skeletal muscle development， which is highly conserved among different species. Animal individuals with abnormally developed muscles can be obtained by natural mutation or manipulation of the gene by gene editing technology. Studies have shown that MSTN gene mutation can affect muscle development through various regulatory approaches. Therefore， the mechanism of MSTN mutation promoting muscle development was reviewed from five aspects， such as myoblast proliferation， differentiation， protein synthesis and catabolism， histone modification and macrophage polarization， in order to provide reference for the production of new materials for agricultural animal breeding and the treatment of major cachexia.

Key words: gene mutation, cell proliferation, protein synthesis, histone modification, macrophage polarization

中图分类号:

高丽, 杨磊, 李光鹏. Myostatin基因突变激发骨骼肌发育机制研究进展[J]. 生物技术进展, 2021, 11(4): 476-482.

Li GAO, Lei YANG, Guangpeng LI. Research Progress on the Mechanism of Skeletal Muscle Development Stimulated by Myostatin Gene Mutation[J]. Current Biotechnology, 2021, 11(4): 476-482.

图/表 1

参考文献 60

1	李光鹏, 白春玲, 魏著英, 等. 黄牛Myostatin基因编辑研究[J]. 内蒙古大学学报(自然科学版), 2020, 51(1):12-32.
2	王鑫, 高广琦, 魏著英, 等. 杂交F1代myostatin基因编辑肉牛的肉质特性分析[J]. 中国牛业科学, 2018, 44(3):1-7.
3	CLOP A, MARCQ F, TAKEDA H, et al.. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep[J]. Nat. Genet., 2006, 38:813-818.
4	MOSHER D S, QUIGNON P, BUSTAMANTE C D, et al.. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs[J/OL]. PLoS Genet., 2007, 3:e79[2021-06-10]. . DOI:10.1371/journal.pgen. 0030079 .
5	BI Y, HUA Z, LIU X, et al.. Isozygous and selectable marker-free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP[J/OL]. Sci. Rep., 2016, 6:31729[2021-06-10]. .
6	WANG X, NIU Y, ZHOU J, et al.. CRISPR/Cas9-mediated MSTN disruption and heritable mutagenesis in goats causes increased body mass[J]. Anim. Genet., 2018, 49(1):43-51.
7	LEE J, KIM D H, LEE K, et al.. Muscle hyperplasia in Japanese quail by single amino acid deletion in MSTN propeptide[J/OL]. Int. J. Mol. Sci., 2020, 21(4): 1504[2021-06-10]. .
8	肖卫华, 陈佩杰, 刘宇. 巨噬细胞在骨骼肌急性损伤修复中的作用研究进展[J]. 中国运动医学杂志, 2014, 33(3):269-274.
9	TAYLOR W E, BHASIN S, ARTAZA J, et al.. Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells[J]. Am. J. Physiol. Endocrinol. Metab., 2001, 280(2):E221-E228.
10	YABLONKA-REUVENI Z. Development and postnatal regulation of adult myoblasts[J]. Microsc. Res. Tech., 1995, 30(5):366-380.
11	刘超武, 杨倬, 赵斌, 等. 逆转录病毒载体介导的RNA干扰稳定抑制肌肉生长抑制素GDF-8的表达[J]. 生物工程学报, 2008(2):250-255.
12	高丽. Myostatin基因编辑牛肌肉卫星细胞成分化过程中DNA甲基化修饰的作用机制研究[D]. 呼和浩特:内蒙古大学, 博士学位论文, 2019.
13	PATEL A K, TRIPATHI A K, PATEL U A, et al.. Myostatin knockdown and its effect on myogenic gene expression program in stably transfected goat myoblasts[J]. In Vitro Cell. Dev. Biol. Anim., 2014, 50(7):587-596.
14	CARLSON M E, HSU M, CONBOY I M. Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells[J]. Nature, 2008, 454(7203):528-532.
15	YANG W, ZHANG Y, LI Y, et al.. Myostatin induces cyclin D1 degradation to cause cell cycle arrest through a phosphatidylinositol 3-kinase/AKT/GSK-3 beta pathway and is antagonized by insulin-like growth factor 1[J]. J. Biol. Chem., 2007, 282(6):3799-3808.
16	WANG K, TANG X, XIE Z, et al.. CRISPR/Cas9-mediated knockout of myostatin in Chinese indigenous Erhualian pigs[J]. Transgenic Res., 2017, 26(6):799-805.
17	YU B, LU R, YUAN Y, et al.. Efficient TALEN-mediated myostatin gene editing in goats[J]. BMC Dev. Biol., 2016, 16(1):26-33.
18	KOLLIAS H D, MCDERMOTT J C. Transforming growth factor-beta and myostatin signaling in skeletal muscle[J]. J. Appl. Physiol., 2008, 104:579-587.
19	ZHU X, TOPOUZIS S, LIANG L F, et al.. Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism[J]. Cytokine, 2004, 26(6):262-272.
20	ZHANG Y N, WANG Y J, BI Y L, et al.. CRISPR/Cas9-mediated sheep MSTN gene knockout and promote sSMSCs differentiation[J]. J. Cell. Biochem., 2019, 120:1794-1806.
21	GAO L, YANG M M, WEI Z Y, et al.. MSTN mutant promotes myogenic differentiation by increasing demethylase TET1 expression via the SMAD2/SMAD3 pathway[J]. Int. J. Biol. Sci., 2020, 16(8):1324-1334.
22	LI R, ZENG W, MA M, et al.. Precise editing of myostatin signal peptide by CRISPR/Cas9 increases the muscle mass of Liang Guang Small Spotted pigs[J]. Transgenic Res., 2020, 29(1):149-163.
23	LIPINA C, KENDALL H, MCPHERRON A C, et al.. Mechanisms involved in the enhancement of mammalian target of rapamycin signaling and hypertrophy in skeletal muscle of myostatin-deficient mice[J]. FEBS Lett., 2010, 584:2403-2408.
24	ROMMEL C, BODINE S C, CLARKE B A, et al.. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways[J]. Nat. Cell Biol., 2001, 3(11):1009-1013.
25	MORISSETTE M R, COOK S A, BURANASOMBATI C, et al.. Myostatin inhibits IGF-I-induced myotube hypertrophy through Akt[J]. Am. J. Physiol. Cell Physiol., 2009, 297(5):1124-1132.
26	TRENDELENBURG A U, MEYER A, ROHNER D, et al.. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size[J]. Am. J. Physiol. Cell Physiol., 2009, 296(6):1258-1270.
27	AMIROUCHE A, DURIEUX A C, BANZET S, et al.. Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle[J]. Endocrinology, 2009, 150(1):286-294.
28	LIPINA C, KENDALL H, MCPHERRON A C, et al.. Mechanisms involved in the enhancement of mammalian target of rapamycin signaling and hypertrophy in skeletal muscle of myostatin-deficient mice[J]. FEBS Lett., 2010, 584(11):2403-2408.
29	SARTORI R, MILAN G, PATRON M, et al.. Smad2 and 3 transcription factors control muscle mass in adulthood[J]. Am. J. Physiol. Cell Physiol., 2009, 296(6):1248-1257.
30	LIU J, PAN M, HUANG D, et al.. Myostatin-1 inhibits cell proliferation by inhibiting the mTOR signal pathway and MRFs, and activating the ubiquitin-proteasomal system in skeletal muscle cells of Japanese flounder Paralichthys olivaceus [J/OL]. Cells, 2020, 9(11):2376[2021-06-10]. .
31	LIU D, QIAO X, GE Z, et al.. IMB0901 inhibits muscle atrophy induced by cancer cachexia through MSTN signaling pathway[J/OL]. Skelet. Muscle, 2019, 9(1):8[2021-06-10]. .
32	HAN H Q, ZHOU X, MITCH W E, et al.. Myostatin/activin pathway antagonism: molecular basis and therapeutic potential[J]. Int. J. Biochem. Cell Biol., 2013, 45(10):2333-2347.
33	GUTTRIDGE D C. A TGF-beta pathway associated with cancer cachexia[J]. Nat. Med., 2015, 21:1248-1249.
34	WANG Y, YAN X, LIU H, et al.. Effect of thermal manipulation during embryogenesis on the promoter methylation and expression of myogenesis-related genes in duck skeletal muscle[J]. J. Therm. Biol., 2019, 80:75-81.
35	JONES T I, KING O D, HIMEDA C L, et al.. Individual epigenetic status of the pathogenic D 4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy[J/OL]. Clin. Epigenet., 2015, 7:37[2021-06-10]. .
36	JONES T I, YAN C, SAPP P C, et al.. Identifying diagnostic DNA methylation profiles for facioscapulohumeral muscular dystrophy in blood and saliva using bisulfite sequencing[J/OL]. Clin. Epigenet., 2014, 6:23[2021-06-10]. .
37	LEMMERS R J, GOEMAN J J, VLIET P JVAN DER, et al.. Inter-individual differences in CpG methylation at D4Z4 correlate with clinical variability in FSHD1 and FSHD2[J]. Hum. Mol. Genet., 2015, 24:659-669.
38	MATTHEW G G, STUART S L, LAURIE A B, et al.. A chromatin landmark and transcription initiation at most promoters in human cells[J]. Cell, 2007,130(1):77-88.
39	WANG S, SUN Y, REN R, et al.. H3K27me3 depletion during differentiation promotes myogenic transcription in porcine satellite cells[J/OL]. Genes, 2019,10:231[2021-06-10]. .
40	ASP P, BLUM R, VETHANTHAM V, et al.. Genome-wide remodeling of the epigenetic landscape during myogenic differentiation[J]. Proc. Natl. Acad. Sci. USA, 2011, 108(22): E149-E158.
41	CARETTI G, DI PADOVA M, MICALES B, et al.. The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation[J]. Genes Dev., 2004,18(21): 2627-2638.
42	WEI C, REN H, XU L, et al.. Signals of Ezh 2, Src, and Akt involve in myostatin-Pax7 pathways regulating the myogenic fate determination during the sheep myoblast proliferation and differentiation[J/OL]. PLoS ONE, 2015, 10(3): e0120956[2021-06-10]. .
43	BYRNE K, MCWILLIAM S, VUOCOLO T, et al.. Genomic architecture of histone 3 lysine 27 trimethylation during late ovine skeletal muscle development[J]. Anim. Genet., 2014, 45(3):427-438.
44	BAAR K. Epigenetic control of skeletal muscle fibre type[J]. Acta Physiol., 2010, 199:477-487.
45	GAO L, YANG M M, WANG X Q, et al.. MSTN knockdown decreases the trans-differentiation from myocytes to adipocytes by reducing Jmjd3 expression via the SMAD2/SMAD3 complex[J]. Biosci. Biotechnol. Biochem., 2019, 83(11):2090-2096.
46	JARVINEN T A, JARVINEN T L, KAARIAINEN M, et al.. Muscle injuries: biology and treatment[J]. Am. J. Sports Med., 2005, 33(5):745-764.
47	CHARGE S B, RUDNICKI M A. Cellular and molecular regulation of muscle regeneration[J]. Physiol. Rev., 2004, 84(1):209-238.
48	MURRAY P J, ALLEN J E, BISWAS S K, et al.. Macrophage activation and polarization: nomenclature and experimental guidelines[J]. Immunity, 2014, 41(1):14-20.
49	郑莉芳, 陈佩杰, 周永战, 等. 老年骨骼肌再生能力受损的机制研究进展[J]. 生理科学进展, 2017, 48(5):393-397.
50	MARTINEZ F O, GORDON S. The M 1 and M2 paradigm of macrophage activation: time for reassessment[J/OL]. F1000Prime Rep., 2014, 6:13[2021-06-10]. . DOI: 10.12703/P6-13 .
51	MILLS C D. Anatomy of a discovery: M1 and M2 macrophages[J/OL]. Front. Immunol., 2015, 6:212[2021-06-10]. .
52	VILLALTA S A, NGUYEN H X, DENG B, et al.. Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy[J]. Hum. Mol. Genet., 2009, 18(3):482-496.
53	TIDBALL J G, VILLALTA S A. Regulatory interactions between muscle and the immune system during muscle regeneration[J]. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2010, 298(5):1173-1187.
54	TIDBALL J G. Mechanisms of muscle injury, repair, and regeneration[J]. Compr. Physiol., 2011, 1(4):2029-2062.
55	BOIS P R, GROSVELD G C. FKHR(FOXO1a) is required for myotube fusion of primary mouse myoblasts[J]. EMBO J., 2003, 22(5):1147-1157.
56	MATTHEW G M, DAVID L H, MARK P, et al.. Inhibition of myostatin signaling through Notch activation following acute resistance exercise[J/OL]. PLoS ONE, 2013, 8(7): e68743[2021-06-10]. .
57	ENDO T. Molecular mechanisms of skeletal muscle development, regeneration, and osteogenic conversion[J]. Bone, 2015, 80:2-13.
58	WOZNIAK A C, PILIPOWICZ O, YABLONKA-REUVENI Z, et al.. C-Met expression and mechanical activation of satellite cells on cultured muscle fibers [J]. J. Histochem. Cytochem., 2003, 51(11):1437-1445.
59	LIPINA C, KENDALL H, MCPHERRON A C, et al.. Mechanisms involved in the enhancement of mammalian target of rapamycin signaling and hypertrophy in skeletal muscle of myostatin-deficient mice[J]. FEBS Lett., 2010, 584:2403-2408.
60	TANG L, AN S, ZHANG Z, et al.. MSTN is a key mediator for low-intensity pulsed ultrasound preventing bone loss in hindlimb-suspended rats[J/OL]. Bone, 2021, 143:115610[2021-06-10]. .

[1]	乌格叶木日, 武建强. 结晶紫的抗肿瘤作用[J]. 生物技术进展, 2025, 15(2): 226-233.
[2]	朱旭, 张英楠, 马金法, 石莉红. Ptbp1在小鼠急性T淋巴细胞白血病中的作用研究[J]. 生物技术进展, 2025, 15(2): 341-348.
[3]	唐颖, 武建强. 肉苁蓉苯乙醇苷的抗肿瘤作用[J]. 生物技术进展, 2023, 13(3): 399-405.
[4]	黄琬玲, 朱文琦, 郭妮妮, 王楠, 任倩, 马小彤. NRG4基因对急性髓系白血病细胞增殖、凋亡及周期的影响[J]. 生物技术进展, 2023, 13(2): 305-310.
[5]	沈云燕, 邱琦. 褪黑素联合顺铂对宫颈癌HeLa细胞增殖、凋亡及侵袭的影响[J]. 生物技术进展, 2023, 13(2): 311-317.
[6]	郭婧雅, 张萍, 赵雨菡, 李梦杰, 黄昆仑, 仝涛. 肥胖诱导的骨骼肌萎缩机制研究进展[J]. 生物技术进展, 2022, 12(6): 861-868.
[7]	孙梦婷, 赵鹏翔, 仪杨, 王濛, 谢飞, ADZAVON Yao Mawulikplimi, 刘梦昱. 二甲双胍对胶质母细胞瘤细胞的抑制作用研究[J]. 生物技术进展, 2022, 12(6): 937-945.
[8]	肖金平, 李程, 曹云娣, 孙志坚, 康平, 兰晓梅. RET原癌基因与肿瘤相关性研究的进展现状[J]. 生物技术进展, 2022, 12(1): 57-62.
[9]	杨梦恬,袁菊懋. RTN4对于结肠癌细胞增殖的调控作用[J]. 生物技术进展, 2021, 11(2): 238-243.
[10]	谷明娟,高丽,王丽荣,李光鹏. 牛无角性状研究进展[J]. 生物技术进展, 2017, 7(3): 177-181.
[11]	路艳,陈莹,陆庆明,张颖,李朝晖,谢晓华 . 大鼠创伤失血性休克心肌巨噬细胞极化标志蛋白变化规律研究[J]. 生物技术进展, 2017, 7(3): 225-229.
[12]	杨芹,陈海琴,陈思,顾震南,张灏,陈永泉,陈卫. 高山被孢霉ω-3脂肪酸脱饱和酶基因在麦胚无细胞蛋白质合成系统中的表达[J]. 生物技术进展, 2016, 6(5): 346-351.
[13]	邓龙,周思,郭新东. 基于基因突变的基因工程抗体亲和力成熟研究[J]. 生物技术进展, 2014, 4(6): 400-404.

Myostatin基因突变激发骨骼肌发育机制研究进展

Research Progress on the Mechanism of Skeletal Muscle Development Stimulated by Myostatin Gene Mutation

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 60

相关文章 13

编辑推荐

Metrics

本文评价