Urotensin II inhibits the proliferation but not the differentiation of cardiac side population cells

Peptides. 2011 May;32(5):1035-41. doi: 10.1016/j.peptides.2011.01.024. Epub 2011 Feb 1.


Urotensin II (UII) induces the development of cardiac remodeling and atherosclerosis by promoting hypertrophy of cardiomyocytes and mitogenesis of fibroblasts and vascular smooth muscle cells. But its effect on cardiac side population cells (CSPs), one of somatic stem cells, is unclear. The present study examined the influences of UII on the differentiation and proliferation of CSPs. CSPs were isolated from neonatal rat hearts by fluorescence-activated cell sorting (FACS) and cultured with or without the presence of UII (10(-8), 10(-7), 10(-6)mol/l). The expressions of α-cardiac myosin heavy chain (α-MHC), α-smooth muscle actin (SMA) and Von Willebrand factor (vWF) mRNAs and proteins were analyzed by reverse transcriptional PCR (RT-PCR) and immunofluorescence to evaluate the differentiation of CSPs into cardiomyocytes, smooth muscle cells and endothelial cells, respectively. The proliferation of CSPs was assessed by Luminescent Cell Viability Assay. The influence of UII on the proliferation of CSPs in vivo was also evaluated by FACS. Our results revealed that UII did inhibit the proliferation of CSPs through up-regulation of phosphorylated c-Jun N-terminal protein kinase (JNK), although it didn't affect the differentiation of cultured CSPs. Experiments in vivo also showed that UII reduced the number of CSPs in mice compared with control group. These data indicate that UII reduces the number of CSPs by inhibiting the proliferation of CSPs possibly through increase of JNK phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Male
  • Mice
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects*
  • Rats
  • Side-Population Cells / cytology*
  • Side-Population Cells / drug effects*
  • Urotensins / pharmacology*


  • Urotensins
  • urotensin II