Skip to main content
SpringerLink
Log in

Decorin Induces Cardiac Hypertrophy by Regulating the CaMKII/MEF-2 Signaling Pathway In Vivo

  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

Objective

Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading, but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure. Cardiac hypertrophy is mostly considered reversible, and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension, but also achieves therapeutic effects by blocking fibrosis-related signaling pathways. However, the mechanism of action of decorin remains unknown and unconfirmed.

Methods

We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight, histological analysis and immunohistochemistry. Western blotting was performed to detect the expression levels of CaMKII, p-CaMKII and MEF-2 in the heart.

Results

Our results confirmed that decorin can regulate the CaMKII/MEF-2 signaling pathway, with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy.

Conclusion

Taken together, the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKII/MEF-2 signaling pathway in vivo, revealing a new therapeutic approach for the prevention of cardiac hypertrophy.

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

Similar content being viewed by others

References

  1. Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol, 2006,7(8):589–600

    Article  CAS  Google Scholar 

  2. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol, 2000,35(3):569–582

    Article  CAS  Google Scholar 

  3. Gradman AH, Alfayoumi F. From left ventricular hypertrophy to congestive heart failure: management of hypertensive heart disease. Prog Cardiovasc Dis, 2006, 48(5):326–341

    Article  Google Scholar 

  4. van Berlo JH, Maillet M, Molkentin JD. Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest, 2013,123(266):37–45

    Article  CAS  Google Scholar 

  5. Koitabashi N, Kass DA. Reverse remodeling in heart failure—mechanisms and therapeutic opportunities. Nat Rev Cardiol, 2011,9(134):147–157

    PubMed  Google Scholar 

  6. Manabe I, Shindo T, Nagai R. Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy. Circ Res, 2002,91(357):1103–1113

    Article  CAS  Google Scholar 

  7. Gabbiani G. The biology of the myofibroblast. Kidney Int, 1992,41(206):530–532

    Article  CAS  Google Scholar 

  8. Zeisberg M, Strutz F, Muller GA. Role of fibroblast activation in inducing interstitial fibrosis. J Nephrol, 2000,13(99):1121–8428

    Google Scholar 

  9. Goldoni S, Owens RT, McQuillan DJ, et al. Biologically active decorin is a monomer in solution. J Biol Chem, 2004,279(86):6606–6612

    Article  CAS  Google Scholar 

  10. Yan W, Wang PC, Tang J, et al. Decorin gene delivery inhibits cardiac fibrosis in spontaneously hypertensive rats by modulation of transforming growth factorbeta/Smad and p38 mitogen-activated protein kinase signaling pathways. Human Gene Therapy, 2009, 20(51):1190–1200

    Article  CAS  Google Scholar 

  11. Kudoh S, Akazawa H, Takano H, et al. Stretch-modulation of second messengers: effects on cardiomyocyte ion transport. Prog Biophys Mol Biol,2003, 82(29):57–66

    Article  CAS  Google Scholar 

  12. Zhang T, Kohlhaas M, Backs J, et al. CaMKIIdelta isoforms differentially affect calcium handling but similarly regulate HDAC/MEF2 transcriptional responses. J Biol Chem, 2007,282(149):35078–35087

    Article  CAS  Google Scholar 

  13. Abdel-Wahab N, Wicks SJ, Mason RM, et al. Decorin suppresses transforming growth factor-beta-induced expression of plasminogen activator inhibitor-1 in human mesangial cells through a mechanism that involves Ca2+-dependent phosphorylation of Smad2 at serine-240. Biochem J, 2002,362(60):643–649

    Article  CAS  Google Scholar 

  14. Wang T, Hou LB, Liu ZJ, et al. Intramuscular delivery of rAAV-mediated kallikrein gene reduces hypertension and prevents cardiovascular injuries in model rats. Acta Pharmacol Sin, 2007,28(6):1898–1906

    Article  CAS  Google Scholar 

  15. Sato K, Suematsu A, Nakashima T, et al. Regulation of osteoclast differentiation and function by the CaMK-CREB pathway. Nat Med, 2006,12(236):1410–1416

    Article  CAS  Google Scholar 

  16. Kompa AR, See F, Lewis DA, et al. Long-term but not short-term p38 mitogen-activated protein kinase inhibition improves cardiac function and reduces cardiac remodeling post-myocardial infarction. J Pharmacol Exp Ther, 2008,325(46):741–750

    Article  CAS  Google Scholar 

  17. Dunkman AA, Buckley MR, Mienaltowski MJ, et al. Decorin expression is important for age-related changes in tendon structure and mechanical properties. Matrix Biol, 2013,32(103):3–13

    Article  CAS  Google Scholar 

  18. Dunkman AA, Buckley MR, Mienaltowski MJ, et al. The injury response of aged tendons in the absence of biglycan and decorin. Matrix Biol, 2014,35(44):232–238

    Article  CAS  Google Scholar 

  19. Schaefer L, Tredup C, Gubbiotti MA, et al. Proteoglycan neofunctions: regulation of inflammation and autophagy in cancer biology. Febs j, 2017,284(78): 10–26

    Article  CAS  Google Scholar 

  20. Horvath Z, Kovalszky I, Fullar A, et al. Decorin deficiency promotes hepatic carcinogenesis. Matrix Biol, 2014,35(50):194–205

    Article  CAS  Google Scholar 

  21. Duncan MB. Extracellular matrix transcriptome dynamics in hepatocellular carcinoma. Matrix Biol, 2013,32(17):393–398

    Article  CAS  Google Scholar 

  22. Patel S, Santra M, McQuillan DJ, et al. Decorin activates the epidermal growth factor receptor and elevates cytosolic Ca2+ in A431 carcinoma cells. J Biol Chem, 1998,273(102):3121–3124

    Article  CAS  Google Scholar 

  23. Wu Z, Horgan CE, Carr O, et al. Biglycan and decorin differentially regulate signaling in the fetal membranes. Matrix Biol, 2014,35(26):266–275

    Article  Google Scholar 

  24. Baghy K, Iozzo RV, Kovalszky I. Decorin-TGFbeta axis in hepatic fibrosis and cirrhosis. J Histochem Cytochem, 2012,60(99):262–268

    Article  CAS  Google Scholar 

  25. Jarvelainen H, Sainio A, Wight TN. Pivotal role for decorin in angiogenesis. Matrix Biol, 2015,43(77):15–26

    Article  CAS  Google Scholar 

  26. Brandan E, Gutierrez J. Role of skeletal muscle proteoglycans during myogenesis. Matrix Biol, 2013, 32(45):289–297

    Article  CAS  Google Scholar 

  27. Barallobre-Barreiro J, Gupta SK, Zoccarato A, et al. Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation. Circulation, 2016,134(26):817–832

    Article  CAS  Google Scholar 

  28. Gronau T, Kruger K, Prein C, et al. Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin. Ann Rheum Dis, 2017,76(19):442–449

    Article  CAS  Google Scholar 

  29. Merline R, Lazaroski S, Babelova A, et al. Decorin deficiency in diabetic mice: aggravation of nephropathy due to overexpression of profibrotic factors, enhanced apoptosis and mononuclear cell infiltration. J Physiol Pharmacol, 2009,60(59):5–13

    PubMed  PubMed Central  Google Scholar 

  30. Iozzo RV, Buraschi S, Genua M, et al. Decorin antagonizes IGF receptor I (IGF-IR) function by interfering with IGF-IR activity and attenuating downstream signaling. J Biol Chem, 2011,286(98):34712–34721

    Article  CAS  Google Scholar 

  31. Morcavallo A, Buraschi S, Xu SQ, et al. Decorin differentially modulates the activity of insulin receptor isoform A ligands. Matrix Biol, 2014,35(35):82–90

    Article  CAS  Google Scholar 

  32. Seidler DG, Mohamed NA, Bocian C, et al. The role for decorin in delayed-type hypersensitivity. J Immunol, 2011,187(40):6108–6119

    Article  CAS  Google Scholar 

  33. Lehmann LH, Worst BC, Stanmore DA, et al. Histone deacetylase signaling in cardioprotection. Cell Mol Life Sci, 2014,71(30):1673–1690

    Article  CAS  Google Scholar 

  34. Kim Y, Phan D, van Rooij E, et al. The MEF2D transcription factor mediates stress-dependent cardiac remodeling in mice. J Clin Invest, 2008,118(159):124–132

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yan Yang, Wei-wei Yu, Wen Yan & Qin Xia

Authors
  1. Yan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei-wei Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qin Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qin Xia.

Ethics declarations

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, Y., Yu, Ww., Yan, W. et al. Decorin Induces Cardiac Hypertrophy by Regulating the CaMKII/MEF-2 Signaling Pathway In Vivo. CURR MED SCI 41, 857–862 (2021). https://doi.org/10.1007/s11596-021-2426-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-021-2426-y

Key words

Search

Navigation