Stem Cell Reviews and Reports

, Volume 15, Issue 1, pp 48–58 | Cite as

Kinin-B2 Receptor Activity in Skeletal Muscle Regeneration and Myoblast Differentiation

  • Janaina M. Alves
  • Antonio H. Martins
  • Claudiana Lameu
  • Talita Glaser
  • Nawal M. Boukli
  • Vinicius Bassaneze
  • Rafael Dariolli
  • Isis C. Nascimento
  • Poliana C. M. Martins
  • Héllio D. N. de Souza
  • José Eduardo Krieger
  • Dulce E. Casarini
  • Vicencia M. Sales
  • João B. Pesquero
  • Henning UlrichEmail author


The bioactive peptide bradykinin obtained from cleavage of precursor kininogens activates the kinin-B2 receptor functioning in induction of inflammation and vasodilatation. In addition, bradykinin participates in kidney and cardiovascular development and neuronal and muscle differentiation. Here we show that kinin-B2 receptors are expressed throughout differentiation of murine C2C12 myoblasts into myotubes. An autocrine loop between receptor activation and bradykinin secretion is suggested, since bradykinin secretion is significantly reduced in the presence of the kinin-B2 receptor antagonist HOE-140 during differentiation. Expression of skeletal muscle markers and regenerative capacity were decreased after pharmacological inhibition or genetic ablation of the B2 receptor, while its antagonism increased the number of myoblasts in culture. In summary, the present work reveals to date no functions described for the B2 receptor in muscle regeneration due to the control of proliferation and differentiation of muscle precursor cells.


Mouse myoblast differentiation Muscle repair Kinin-B2 receptor HOE-140 



This work was supported by grants awarded by Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo Research Foundation, FAPESP, Project No. 2012/50880-4) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), Brazil, to H.U. and C.L. (2015/19128-2), by a NIH grant, to A.H.M (8G12MD007600) and by the Universidad Central del Caribe Biomedical Proteomics Facility Grant G12MD007583 awarded to NMB from the NIH National Institute on Minority Health and Health Disparities (NIMHD) RCMI Program.. J.M.A.’s Ph.D. thesis research was funded by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), Brazil. This study was financed by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Brazil (CAPES) – Finance Code 001.

Compliance with Ethical Standards

Conflict of Interest

All authors declare that they do not have conflict of interests of any type to publish the manuscript.

Supplementary material

12015_2018_9850_MOESM1_ESM.docx (1 mb)
ESM 1 (DOCX 1.01 mb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Janaina M. Alves
    • 1
    • 2
  • Antonio H. Martins
    • 3
    • 4
  • Claudiana Lameu
    • 4
  • Talita Glaser
    • 4
  • Nawal M. Boukli
    • 5
  • Vinicius Bassaneze
    • 6
  • Rafael Dariolli
    • 6
  • Isis C. Nascimento
    • 1
    • 4
  • Poliana C. M. Martins
    • 4
  • Héllio D. N. de Souza
    • 4
  • José Eduardo Krieger
    • 6
  • Dulce E. Casarini
    • 6
  • Vicencia M. Sales
    • 7
  • João B. Pesquero
    • 7
  • Henning Ulrich
    • 4
    Email author
  1. 1.Departmento de Neurologia/NeurocirurgiaUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Department of Microbiology and ImmunologyUniversidad Central del CaribeBayamónUSA
  3. 3.Pharmacology and Toxicology DepartmentUniversity of Puerto Rico Medical -Sciences CampusRio PiedrasUSA
  4. 4.Departamento de Bioquímica, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil
  5. 5.Biomedical Proteomics Facility, Department of Microbiology and ImmunologyUniversidad Central del CaribeBayamónUSA
  6. 6.Heart Institute (InCor)University of São Paulo Medical SchoolSão PauloBrazil
  7. 7.Departamento de BiofísicaUniversidade Federal de São PauloSão PauloBrazil

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