In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 18, No. 5 ( 2014-05), p. 852-862
Abstract:
Cardiac side population cells ( CSP s) are promising cell resource for the regeneration in diseased heart as intrinsic cardiac stem cells. However, the relative low ratio of CSP s in the heart limited the ability of CSP s to repair heart and improve cardiac function effectively under pathophysiological condition. Which factors limiting the proliferation of CSP s in diseased heart are unclear. Here, we show that urotensin II (UII) regulates the proliferation of CSP s by c‐Jun N ‐terminal kinase ( JNK ) and low density lipoprotein receptor‐related protein 6 ( LRP 6) signalling during pressure overload. Pressure overload greatly upregulated UII level in plasma, UII receptor ( UT ) antagonist, urantide, promoted CSP s proliferation and improved cardiac dysfunction during chronic pressure overload. In cultured CSP s subjected to mechanical stretch ( MS ), UII significantly inhibited the proliferation by UT . Nanofluidic proteomic immunoassay showed that it is the JNK activation, but not the extracellular signal‐regulated kinase signalling, that involved in the UII‐inhibited‐ proliferation of CSP s during pressure overload. Further analysis in vitro indicated UII‐induced‐phospho‐ JNK regulates phosphorylation of LRP 6 in cultured CSP s after MS , which is important in the inhibitory effect of UII on the CSP s during pressure overload. In conclusion, UII inhibited the proliferation of CSP s by JNK / LRP 6 signalling during pressure overload. Pharmacological inhibition of UII promotes CSP s proliferation in mice, offering a possible therapeutic approach for cardiac failure induced by pressure overload.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2014.18.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2076114-4
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