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

Stem Cell Rev Rep. 2019 Feb;15(1):48-58. doi: 10.1007/s12015-018-9850-9.


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.

Keywords: HOE-140; Kinin-B2 receptor; Mouse myoblast differentiation; Muscle repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bradykinin / metabolism
  • Cardiotoxins / administration & dosage
  • Cell Differentiation*
  • Cell Line
  • Cell Proliferation
  • Cytoskeleton / metabolism
  • Gene Deletion
  • Kininogens / genetics
  • Kininogens / metabolism
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / physiology*
  • Myoblasts / cytology*
  • Myosin Heavy Chains / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Bradykinin B2 / genetics
  • Receptor, Bradykinin B2 / metabolism*
  • Regeneration*


  • Biomarkers
  • Cardiotoxins
  • Kininogens
  • RNA, Messenger
  • Receptor, Bradykinin B2
  • Myosin Heavy Chains
  • Bradykinin