Skip to main content
SpringerLink
Log in

ISLR regulates skeletal muscle atrophy via IGF1-PI3K/Akt-Foxo signaling pathway

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Immunoglobulin superfamily containing leucine-rich repeat (Islr) contains an Ig-like domain, an LRR motif, and a transmembrane domain and is highly expressed in various chicken tissues. Although Islr has known roles in muscle regeneration, its role in the regulation of muscle atrophy has not been studied. In this study, we constructed Islr-silenced or Islr-overexpressed myoblasts to investigate its role during the differentiation of myoblasts into myotubes. The results showed that Islr was highly expressed in chicken skeletal muscle tissue and regulated myoblast differentiation, but not proliferation. Islr regulated the expression of atrophy-related genes including atrogin-1 and MuRF-1, and could rescue dexamethasone-induced atrophy in myoblasts and myotubes. Western blot analysis indicated that Islr participates in myoblast atrophy through IGF/PI3K/AKT-FOXO signaling. Meanwhile, the expression of caspase-8 and caspase-9 increased in Islr-silenced groups, indicating its role in cell viability. Taken together, these data suggested that Islr plays an important role in myoblasts differentiation, and which can alleviate skeletal muscle atrophy and prevents muscle cell apoptosis via IGF/PI3K/AKT-FOXO signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Bodine SC, Latres E, Baumhueter S, Lai VK-M, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294(5547):1704–1708

    CAS  PubMed  Google Scholar 

  • Bulfield G, Siller W, Wight P, Moore KJ (1984) X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci 81(4):1189–1192

    CAS  PubMed  Google Scholar 

  • Chang NC, Chevalier FP, Rudnicki MA (2016) Satellite cells in muscular dystrophy–lost in polarity. Trends Mol Med 22(6):479–496

    CAS  PubMed  PubMed Central  Google Scholar 

  • Charge SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84(1):209–238

    CAS  PubMed  Google Scholar 

  • Devol DL, Rotwein P, Sadow JL, Novakofski J, Bechtel PJ (1990) Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth. Am J Physiol Endocrinol Metab 259(1):E89–E95

    CAS  Google Scholar 

  • Fuster G, Busquets S, Almendro V, López-Soriano FJ, Argilés JM (2007) Antiproteolytic effects of plasma from hibernating bears: a new approach for muscle wasting therapy? Clin Nutr 26(5):658–661

    CAS  PubMed  Google Scholar 

  • Glass DJ (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37(10):1974–1984

    CAS  PubMed  Google Scholar 

  • Glass DJ (2010) PI3 kinase regulation of skeletal muscle hypertrophy and atrophy. In: Phosphoinositide 3-kinase in health and disease. Springer, pp 267-278

  • Goldspink DF, Garlick PJ, McNurlan M (1983) Protein turnover measured in vivo and in vitro in muscles undergoing compensatory growth and subsequent denervation atrophy. Biochem J 210(1):89–98

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gussoni E, Blau HM, Kunkel LM (1997) The fate of individual myoblasts after transplantation into muscles of DMD patients. Nat Med 3(9):970

    CAS  PubMed  Google Scholar 

  • Han S, Cui C, Wang Y, He H, Shen X, Chen Y, Liu Z, Zhu Q, Li D, Yin H (2019) FHL3 negatively regulates the differentiation of skeletal muscle satellite cells in chicken. 3. Biotech 9(6):206

    CAS  Google Scholar 

  • Hasty P, Bradley A, Morris JH, Edmondson DG, Venuti JM, Olson EN, Klein WH (1993) Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature 364(6437):501

    CAS  PubMed  Google Scholar 

  • Jagoe RT, Goldberg AL (2001) What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? Curr Opin Clin Nutr Metab Care 4(3):183–190

    CAS  PubMed  Google Scholar 

  • Knapp JR, Davie JK, Myer A, Meadows E, Olson EN, Klein WH (2006) Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size. Development 133(4):601–610

    CAS  PubMed  Google Scholar 

  • Kress JP, Hall JB (2014) ICU-acquired weakness and recovery from critical illness. N Engl J Med 370(17):1626–1635

    CAS  PubMed  Google Scholar 

  • Latres E, Amini AR, Amini AA, Griffiths J, Martin FJ, Wei Y, Lin HC, Yancopoulos GD, Glass DJ (2005) Insulin-like growth factor-1 (IGF-1) inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem 280(4):2737–2744

    CAS  PubMed  Google Scholar 

  • Li Z, Cai B, Abdalla BA, Zhu X, Zheng M, Han P, Nie Q, Zhang X (2019) LncIRS1 controls muscle atrophy via sponging miR-15 family to activate IGF1-PI3K/AKT pathway. J Cachexia Sarcopenia Muscle 10(2):391–410

    PubMed  PubMed Central  Google Scholar 

  • Liao R, Yan F, Zeng Z, Farhan M, Little P, Quirion R et al (2017) Amiodarone-induced retinal neuronal cell apoptosis attenuated by igf-1 via counter regulation of the pi3k/akt/foxO3a pathway. Mol Neurobiol 54(9):6931–6943

    CAS  PubMed  Google Scholar 

  • Liu XZ, Fan J, Qi K, Liu SP, Xu WD, Gao Y, Gu XD, Li J, Bai CG, Shi YQ (2017) Dishevelled2 promotes apoptosis and inhibits inflammatory cytokine secretion in rheumatoid arthritis fibroblast-like synoviocytes through crosstalk with the NF-κB pathway. Oncotarget 8(8):12649

    PubMed  PubMed Central  Google Scholar 

  • Luo W, Chen J, Li L, Ren X, Cheng T, Lu S, Lawal RA, Nie Q, Zhang X, Hanotte O (2019) c-Myc inhibits myoblast differentiation and promotes myoblast proliferation and muscle fibre hypertrophy by regulating the expression of its target genes, miRNAs and lincRNAs. Cell Death Differ 26(3):426

    CAS  PubMed  Google Scholar 

  • Maddock D, Burton M (1994) Some effects of starvation on the lipid and skeletal muscle layers of the winter flounder, Pleuronectes americanus. Can J Zool 72(9):1672–1679

    CAS  Google Scholar 

  • Maeda K, Enomoto A, Hara A, Asai N, Kobayashi T, Horinouchi A, Maruyama S, Ishikawa Y, Nishiyama T, Kiyoi H (2016) Identification of Meflin as a potential marker for mesenchymal stromal cells. Sci Rep 6:22288

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meadows E, Cho J-H, Flynn JM, Klein WH (2008) Myogenin regulates a distinct genetic program in adult muscle stem cells. Dev Biol 322(2):406–414

    CAS  PubMed  Google Scholar 

  • Milan G, Romanello V, Pescatore F, Armani A, Paik J-H, Frasson L, Seydel A, Zhao J, Abraham R, Goldberg AL (2015) Regulation of autophagy and the ubiquitin–proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun 6:6670

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nagasawa A, Kubota R, Imamura Y, Nagamine K, Wang Y, Asakawa S, Kudoh J, Minoshima S, Mashima Y, Oguchi Y (1997) Cloning of the cDNA for a new member of the immunoglobulin superfamily (ISLR) containing leucine-rich repeat (LRR). Genomics 44(3):273–279

    CAS  PubMed  Google Scholar 

  • Nagasawa A, Kudoh J, Noda S, Mashima Y, Wright A, Oguchi Y, Shimizu N (1999) Human and mouse ISLR (immunoglobulin superfamily containing leucine-rich repeat) genes: genomic structure and tissue expression. Genomics 61(1):37–43

    CAS  PubMed  Google Scholar 

  • Pereira JASA, Wessels A, Nijtmans L, Moorman AF, Sargeant AJ (1995) New method for the accurate characterization of single human skeletal muscle fibres demonstrates a relation between mATPase and MyHC expression in pure and hybrid fibre types. J Muscle Res Cell Motil 16(1):21–34

    CAS  Google Scholar 

  • Povsic TJ, Kohout TA, Lefkowitz RJ (2003) β-Arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis. J Biol Chem 278(51):51334–51339

    CAS  PubMed  Google Scholar 

  • Powers SK, Morton AB, Ahn B, Smuder AJ (2016) Redox control of skeletal muscle atrophy. Free Radic Biol Med 98:208–217

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sacco A, Mourkioti F, Tran R, Choi J, Llewellyn M, Kraft P, Shkreli M, Delp S, Pomerantz JH, Artandi SE (2010) Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell 143(7):1059–1071

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL (2004) IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab 287(4):E591–E601

    CAS  PubMed  Google Scholar 

  • Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL (2004) Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117(3):399–412

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sartorelli V, Fulco M (2004) Molecular and cellular determinants of skeletal muscle atrophy and hypertrophy. Sci STKE 2004(244):re11

    PubMed  Google Scholar 

  • Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M, Yancopoulos GD, Glass DJ (2004) The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 14(3):395–403

    CAS  PubMed  Google Scholar 

  • Yablonka-Reuveni Z, Paterson BM (2001) MyoD and myogenin expression patterns in cultures of fetal and adult chicken myoblasts. J Histochem Cytochem 49(4):455–462

    CAS  PubMed  Google Scholar 

  • Zhang Y, Li W, Zhu M, Li Y, Xu Z, Zuo B (2016) FHL3 differentially regulates the expression of MyHC isoforms through interactions with MyoD and pCREB. Cell Signal 28(1):60–73

    CAS  PubMed  Google Scholar 

  • Zhang K, Zhang Y, Gu L, Lan M, Liu C, Wang M, Su Y, Ge M, Wang T, Yu Y (2018) Islr regulates canonical Wnt signaling-mediated skeletal muscle regeneration by stabilizing Dishevelled-2 and preventing autophagy. Nat Commun 9(1):5129

    PubMed  PubMed Central  Google Scholar 

  • Zhao W, Pan J, Zhao Z, Wu Y, Bauman WA, Cardozo CP (2008) Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. J Steroid Biochem Mol Biol 110(1–2):125–129

    CAS  PubMed  Google Scholar 

Download references

Funding

This research was supported by the Sichuan Science and Technology Program (2018JY0488) and the China Agriculture Research System (CARS-40-K06).

Author information

Authors and Affiliations

  1. Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People’s Republic of China

    Can Cui, Shunshun Han, Xiaoxu Shen, Haorong He, Yuqi Chen, Jing Zhao, Yuanhang Wei, Yan Wang, Qing Zhu, Diyan Li & Huadong Yin

Authors
  1. Can Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shunshun Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoxu Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haorong He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuqi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuanhang Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Qing Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Diyan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Huadong Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, CC, SH, and HY; data curation, CC and SH; formal analysis, CC, SH, JZ, and DL; funding acquisition, QZ and HY; investigation, SH, CC, HH, XS, YW, and YC; project administration, YW and HY; resources, HY; supervision, HY; writing—original draft, SH and CC; writing—review and editing, HY.

Corresponding author

Correspondence to Huadong Yin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics statement

All experimental procedures in the present study complied with the recommendations of the Animal Care and Use Committee of Sichuan Agricultural University, and the study was approved by the Animal Care and Use Committee of Sichuan Agricultural University (Sichuan, China) under permit number: YCS-2018-10200601.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 21 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cui, C., Han, S., Shen, X. et al. ISLR regulates skeletal muscle atrophy via IGF1-PI3K/Akt-Foxo signaling pathway. Cell Tissue Res 381, 479–492 (2020). https://doi.org/10.1007/s00441-020-03251-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-020-03251-4

Keywords

Search

Navigation