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

作者:Gong Hui; Ma Hong; Liu Meilan; Zhou Bojiang; Zhang Guoping; Chen Zhidan; Jiang Guoliang; Yan Yuan; Yang Chunjie; Kanda Masato; Wu Jian; Yuan Jie; Li Lei; Nagai Toshio; Komuro Issei; Ge Junbo; Zou Yunzeng*
来源:Peptides, 2011, 32(5): 1035-1041.
DOI:10.1016/j.peptides.2011.01.024

摘要

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 Ull (10(-8). 10(-7), 10(-6) mol/l). The expressions of a-cardiac myosin heavy chain (alpha-MHC), a-smooth muscle actin (SMA) and Von Willebrand factor (vWF) mRNAs and proteins were analyzed by reverse transcriptional PCR (RT-PCR) and immunofluoresence 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 (INK), 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.

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