综述 REVIEW

R-spondin1调控骨骼肌生长机制的研究进展

  • 许涛 ,
  • 叶茂 ,
  • 金成龙 ,
  • 王修启
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  • 华南农业大学动物科学学院, 广东省动物营养调控重点实验室, 国家生猪种业工程技术研究中心, 广州 510642
许涛(1997-),男,河南周口人,硕士研究生,从事动物营养与饲料科学研究。E-mail:528950797@qq.com

收稿日期: 2021-05-25

  网络出版日期: 2021-12-16

基金资助

中国博士后科学基金第68批面上项目(2020M682734)

Research Progress of Mechanism of R-Spondin1 Controlling Skeletal Muscle Growth

  • XU Tao ,
  • YE Mao ,
  • JIN Chenglong ,
  • WANG Xiuqi
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  • College of Animal Science, South China Agricultural University, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China

Received date: 2021-05-25

  Online published: 2021-12-16

摘要

骨骼肌是机体的重要组成部分,Wnt信号网络则是调控其生长的主要枢纽。研究表明,R-spondin1作为Wnt信号网络的增强子,对骨骼肌稳态调节有重要作用。但是,R-spondin1参与其生长的功能和作用机制尚未完全阐明。近期研究发现R-spondin1可介导卫星细胞调控骨骼肌损伤修复,且该过程与Wnt信号网络平衡有关。此外,Wnt信号网络功能发挥具有整体性,而骨骼肌生长对其时序性表达有严格要求。因此,研究R-spondin1调控Wnt信号网络对骨骼肌生长的作用机制,对增强动物生肌潜力具有重要意义。本文综述了R-spondin1参与经典和非经典Wnt信号通路调控骨骼肌生长的功能,期望通过梳理R-spondin1作用机理以寻找新的研究靶点,为骨骼肌生长调控提供理论依据。

本文引用格式

许涛 , 叶茂 , 金成龙 , 王修启 . R-spondin1调控骨骼肌生长机制的研究进展[J]. 动物营养学报, 2021 , 33(12) : 6648 -6655 . DOI: 10.3969/j.issn.1006-267x.2021.12.006

Abstract

Skeletal muscle is an important part of the organism, and the Wnt signaling network is the main pivot that regulates its growth. The research showed that R-spondin1, as an enhancer of Wnt signaling network, plays an important role in skeletal muscle steady state regulation. However, the function and mechanism of R-spondin1 participation in its growth has not yet been fully clarified. Recent studies have found that R-spondin1 can mediate satellite cells to regulate skeletal muscle damage and repair, and that the process is related to the balance of the Wnt signaling network. In addition, Wnt signaling network functions are integrated, and skeletal muscle growth have strict requirements for its sequential expression. Therefore, studying the mechanism of R-spondin1 regulating the Wnt signaling network on the growth of skeletal muscle is of great significance for enhancing the myogenic potential of animals. This article reviews the function by which R-spondin1 participates in classical and non-classical Wnt signaling pathways to regulate skeletal muscle growth, and hopes to find new research targets by combing the mechanism of R-spondin1, which can provide theoretical basis for skeletal muscle growth regulation.

参考文献

[1] 李伯江,李平华,吴望军,等.骨骼肌肌纤维形成机制的研究进展[J].中国农业科学,2014(6):1200-1207. LI B J,LI P H,WU W J,et al.Progresses in research of the mechanisms of skeletal muscle fiber formation[J].Scientia Agricultura Sinica,2014(6):1200-1207.(in Chinese)
[2] POLESSKAYA A,SEALE P,RUDNICKI M A.Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration[J].Cell,2003,113(7):841-852.  
[3] RUDOLF A,SCHIRWIS E,GIORDANI L,et al.β-catenin activation in muscle progenitor cells regulates tissue repair[J].Cell Reports,2016,15(6):1277-1290.  
[4] PARISI A,LACOUR F,GIORDANI L,et al.APC is required for muscle stem cell proliferation and skeletal muscle tissue repair[J].The Journal of Cell Biology,2015,210(5):717-726.  
[5] GIRARDI F,LE GRAND F.Chapter five-Wnt signaling in skeletal muscle development and regeneration[J].Progress in Molecular Biology and Translational Science,2018,153:157-179.
[6] XU C F,LIU Y J,WANG Y,et al.Downregulation of R-spondin1 contributes to mechanical stretch-induced lung injury[J].Critical Care Medicine,2019,47(7):e587-e596.
[7] LIN Y,FANG Z P,LIU H J,et al.HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5+ liver stem cells[J].Nature Communications,2017,8:1175.
[8] CHEN W,JU S W,LU T,et al.Directional delivery of RSPO1 by mesenchymal stem cells ameliorates radiation-induced intestinal injury[J].Cytokine,2017,95:27-34.
[9] WEBER E L,LAI Y C,LEI M X,et al.Human fetal scalp dermal papilla enriched genes and the role of R-spondin-1 in the restoration of hair neogenesis in adult mouse cells[J].Frontiers in Cell and Developmental Biology,2020,8:583434.
[10] HAN X H,JIN Y R,SETO M,et al.A Wnt/β-catenin signaling activator,R-spondin,plays positive regulatory roles during skeletal myogenesis[J].Journal of Biological Chemistry,2011,286(12):10649-10659.  
[11] WANG Y X,RUDNICKI M A.Satellite cells,the engines of muscle repair[J].Nature Reviews Molecular Cell Biology,2012,13(2):127-133.  
[12] LE GRAND F,JONES A E,SEALE V,et al.Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells[J].Cell Stem Cell,2009,4(6):535-547.  
[13] SCHMIDT M,SCHVLER S C,HVTTNER S S,et al.Adult stem cells at work:regenerating skeletal muscle[J].Cellular and Molecular Life Sciences,2019,76(13):2559-2570.  
[14] LEPPER C,PARTRIDGE T A,FAN C M.An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration[J].Development,2011,138(17):3639-3646.  
[15] 叶茂,宋志文,金成龙,等.骨骼肌生长发育及再生过程中Wnt信号网络的作用机制[J].动物营养学报,2020,32(8):3560-3567. YE M,SONG Z W,JIN C L,et al.Mechanism of Wnt signaling network in skeletal muscle growth,development and regeneration[J].Chinese Journal of Animal Nutrition,2020,32(8):3560-3567.(in Chinese)
[16] 张宗明,金成龙,严会超,等.Wnt信号调控骨骼肌生长、发育与再生的机制[J].动物营养学报,2019,31(2):560-566. ZHANG Z M,JIN C L,YAN H C,et al.Regulatory mechanism of Wnt signaling in skeletal muscle growth,development and regeneration[J].Chinese Journal of Animal Nutrition,2019,31(2):560-566.(in Chinese)
[17] CHEN X L,LUO Y L,JIA G,et al.The effect of arginine on the Wnt/β-catenin signaling pathway during porcine intramuscular preadipocyte differentiation[J].Food & Function,2017,8(1):381-386.  
[18] 闫研,张军芳,孙斌,等.添加环格列酮对延边黄牛骨骼肌卫星细胞成脂转分化的影响[J].中国畜牧兽医,2020,47(3):714-721. YAN Y,ZHANG J F,SUN B,et al.Effect of ciglitazone on adipogenic transdifferentiation of skeletal muscle satellite cells in Yanbian yellow cattle[J].China Animal Husbandry & Veterinary Medicine,2020,47(3):714-721.(in Chinese)
[19] ZHANG Z M,GAO C Q,YAN H C,et al.Wnt/β-catenin pathway is required for porcine satellite cell proliferation and differentiation to promote skeletal muscle growth[J].Journal of Animal Science,2019,97(S3):97-97.
[20] YANG Y J,YANG J Z,LIU R X,et al.Accumulation of β-catenin by lithium chloride in porcine myoblast cultures accelerates cell differentiation[J].Molecular Biology Reports,2011,38(3):2043-2049.  
[21] BENTZINGER C F,VON MALTZAHN J,DUMONT N A,et al.Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength[J].The Journal of Cell Biology,2014,205(1):97-111.  
[22] VON MALTZAHN J,RENAUD J M,PARISE G,et al.Wnt7a treatment ameliorates muscular dystrophy[J].Proceedings of the National Academy of Sciences of the United States of America,2012,109(50):20614-20619.  
[23] BRACK A S,CONBOY I M,CONBOY M J,et al.A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis[J].Cell Stem Cell,2008,2(1):50-59.  
[24] PENG S J,SONG C C,LI H,et al.Circular RNA SNX29 sponges miR-744 to regulate proliferation and differentiation of myoblasts by activating the Wnt5a/Ca2+ signaling pathway[J].Molecular Therapy:Nucleic Acids,2019,16:481-493.
[25] DE LAU W B M,SNEL B,CLEVERS H C.The R-spondin protein family[J].Genome Biology,2012,13(3):242.
[26] KIM K A,ZHAO J S,ANDARMANI S,et al.R-spondin proteins:a novel link to β-catenin activation[J].Cell Cycle,2006,5(1):23-26.  
[27] KIM K A,WAGLE M,TRAN K,et al.R-spondin family members regulate the Wnt pathway by a common mechanism[J].Molecular Biology of the Cell,2008,19(6):2588-2596.  
[28] PARMA P,RADI O,VIDAL V,et al.R-spondin1 is essential in sex determination,skin differentiation and malignancy[J].Nature Genetics,2006,38(11):1304-1309.  
[29] YAN K S,JANDA C Y,CHANG J L,et al.Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal[J].Nature,2017,545(7653):238-242.  
[30] NAM J S,TURCOTTE T J,YOON J K.Dynamic expression of R-spondin family genes in mouse development[J].Gene Expression Patterns,2007,7(3):306-312.  
[31] LI N,LIU S,ZHANG H S,et al.Exogenous R-spondin1 induces precocious telogen-to-anagen transition in mouse hair follicles[J].International Journal of Molecular Sciences,2016,17(4):582.
[32] SHI G X,ZHENG X F,ZHU C,et al.Evidence of the role of R-spondin 1 and its receptor Lgr4 in the transmission of mechanical stimuli to biological signals for bone formation[J].International Journal of Molecular Sciences,2017,18(3):564.
[33] GORE A V,SWIFT M R,CHA Y R,et al.Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3[J].Development,2011,138(22):4875-4886.  
[34] CHAHAL J K,WONG V S C,CHABOISSIER M C,et al.R-spondin1 deficiency enhances β-cell neogenesis in a murine model of diabetes[J].Pancreas,2014,43(1):93-102.  
[35] NAM J S,PARK E,TURCOTTE T J,et al.Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb[J].Developmental Biology,2007,311(1):124-135.  
[36] BELL S M,SCHREINER C M,WERT S E,et al.R-spondin 2 is required for normal laryngeal-tracheal,lung and limb morphogenesis[J].Development,2008,135(6):1049-1058.  
[37] CADIEU E,NEFF M W,QUIGNON P,et al.Coat variation in the domestic dog is governed by variants in three genes[J].Science,2009,326(5949):150-153.  
[38] AOKI M,MIEDA M,IKEDA T,et al.R-spondin3 is required for mouse placental development[J].Developmental Biology,2007,301(1):218-226.  
[39] KAZANSKAYA O,OHKAWARA B,HEROULT M,et al.The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development[J].Development,2008,135(22):3655-3664.  
[40] BERGMANN C,SENDEREK J,ANHUF D,et al.Mutations in the gene encoding the Wnt-signaling component R-spondin 4(RSPO4) cause autosomal recessive anonychia[J].American Journal of Human Genetics,2006,79(6):1105-1109.  
[41] CROCE J C,MCCLAY D R.Evolution of the Wnt pathways[J].Methods in Molecular Biology,2008,469:3-18.
[42] KOO B K,SPIT M,JORDENS I,et al.Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors[J].Nature,2012,488(7413):665-669.  
[43] HAO H X,XIE Y,ZHANG Y,et al.ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner[J].Nature,2012,485(7397):195-200.  
[44] NAGANO K.R-spondin signaling as a pivotal regulator of tissue development and homeostasis[J].The Japanese Dental Science Review,2019,55(1):80-87.  
[45] CARMON K S,LIN Q S,GONG X,et al.LGR5 interacts and cointernalizes with Wnt receptors to modulate Wnt/β-catenin signaling[J].Molecular and Cellular Biology,2012,32(11):2054-2064.  
[46] BEJSOVEC A.Wnt pathway activation:new relations and locations[J].Cell,2005,120(1):11-14.
[47] GORDON M D,NUSSE R.Wnt signaling:multiple pathways,multiple receptors,and multiple transcription factors[J].Journal of Biological Chemistry,2006,281(32):22429-22433.  
[48] CHEN C,XIANG H,PENG Y L,et al.Mature miR-183,negatively regulated by transcription factor GATA3,promotes 3T3-L1 adipogenesis through inhibition of the canonical Wnt/β-catenin signaling pathway by targeting LRP6[J].Cellular Signalling,2014,26(6):1155-1165.  
[49] MAO B Y,WU W,DAVIDSON G,et al.Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling[J].Nature,2002,417(6889):664-667.  
[50] BINNERTS M E,KIM K A,BRIGHT J M,et al.R-spondin1 regulates Wnt signaling by inhibiting internalization of LRP6[J].Proceedings of the National Academy of Sciences,2007,104(37):14700-14705.  
[51] WEI Q O,YOKOTA C,SEMENOV M V,et al.R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and β-catenin signaling[J].Journal of Biological Chemistry,2007,282(21):15903-15911.  
[52] SUN T L,ANNUNZIATO S,BERGLING S,et al.ZNRF3 and RNF43 cooperate to safeguard metabolic liver zonation and hepatocyte proliferation[J/OL].Cell Stem Cell,2021:S1934-5909(21)00250.(2021-06-11).https://pubmed.ncbi.nlm.nih.gov/34129813.DOI:10.1016/j.stem.2021.05.013.
[53] CARMON K S,GONG X,LIN Q S,et al.R-spondins function as ligands of the orphan receptors Lgr4 and Lgr5 to regulate Wnt/beta-catenin signaling[J].Proceedings of the National Academy of Sciences of the United States of America,2011,108(28):11452-11457.  
[54] DE LAU W,BARKER N,LOW T Y,et al.Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling[J].Nature,2011,476(7360):293-297.  
[55] PARK S,CUI J,YU W S,et al.Differential activities and mechanisms of the four R-spondins in potentiating Wnt/β-catenin signaling[J].Journal of Biological Chemistry,2018,293(25):9759-9769.  
[56] GLINKA A,DOLDE C,KIRSCH N,et al.Lgr4 and Lgr5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling[J].EMBO Reports,2011,12(10):1055-1061.  
[57] LEUNG C,MURAD K B A,TAN A L T,et al.Lgr5 marks adult progenitor cells contributing to skeletal muscle regeneration and sarcoma formation[J].Cell Reports,2020,33(12):108535.
[58] CARMON K S,GONG X,YI J,et al.RSPO-Lgr4 functions via IQGAP1 to potentiate Wnt signaling[J].Proceedings of the National Academy of Sciences of the United States of America,2014,111(13):E1221-E1229.
[59] LACOUR F,VEZIN E,BENTZINGER C F,et al.R-spondin1 controls muscle cell fusion through dual regulation of antagonistic Wnt signaling pathways[J].Cell Reports,2017,18(10):2320-2330.  
[60] TAJBAKHSH S,BORELLO U,VIVARELLI E,et al.Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5[J].Development,1998,125(21):4155-4162.  
[61] JONES A E,PRICE F D,LE GRAND F,et al.Wnt/β-catenin controls follistatin signalling to regulate satellite cell myogenic potential[J].Skeletal Muscle,2015,5:14.
[62] VON MALTZAHN J,BENTZINGER C F,RUDNICKI M A.Wnt7a-Fzd7 signalling directly activates the Akt/mTOR anabolic growth pathway in skeletal muscle[J].Nature Cell Biology,2012,14(2):186-191.  
[63] 朱秋杰.猪RSPO1基因克隆表达及功能验证[D].硕士学位论文.广州:华南农业大学,2020. ZHU Q J.Cloning expression and function verification of RSPO1 gene for pigs[D].Master's Thesis.Guangzhou:South China Agricultural University,2020.
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