Down-regulation of the M6P/IGF-II receptor increases cell proliferation and reduces apoptosis in neonatal rat cardiac myocytes.
Down-regulation of the M6P/IGF-II receptor increases cell proliferation and reduces apoptosis in neonatal rat cardiac myocytes.
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DOI：
10.1186/1471-2121-5-15
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发表时间：
2004-04-28
期刊：
影响因子：
--
通讯作者：
Kang JX
中科院分区：
文献类型：
--
作者：
Chen Z;Ge Y;Kang JX
甘露糖6-磷酸/胰岛素样生长因子- ii受体（M6P/IGF2R）是一种参与细胞生长和凋亡调节的多功能蛋白。心肌细胞表达相对较高水平的M6P/IGF2R，心肌细胞凋亡已在多种心血管疾病中被发现，如心肌梗死和心力衰竭。然而，M6P/IGF2R参与这些疾病的发病机制尚未确定。因此，本研究的目的是确定M6P/IGF2R在心肌细胞生长和凋亡调控中的作用。下调M6P/IGF2R在新生大鼠心肌细胞中的表达，观察其对心肌细胞增殖和凋亡的影响。通过RT-PCR和核糖核酸酶保护试验（RPA）发现，用表达针对M6P/IGF2R的核酶的腺病毒感染新生儿心肌细胞可显著降低M6P/IGF2R mRNA的水平。含M6P蛋白的结合和内吞作用以及M6P/IGF2R介导的125I-IGF-II内化在核酶处理的细胞中比对照肌细胞低，表明核酶处理的细胞中功能M6P/IGF2R的数量减少。因此，在核酶处理的细胞中观察到细胞增殖明显增加，细胞对缺氧和tnf诱导的凋亡的易感性降低。这些发现提示M6P/IGF2R可能参与心肌细胞生长和凋亡的调控。心脏组织中该基因的下调可能是预防某些心脏疾病细胞死亡或促进有丝分裂发生的新途径。
The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) is a multi-functional protein that has been implicated in regulation of cell growth and apoptosis. Cardiac myocytes express relatively high levels of M6P/IGF2R, and cardiomyocyte apoptosis has been identified in a variety of cardiovascular disorders, such as myocardial infarction and heart failure. However, involvement of M6P/IGF2R in the pathogenesis of these conditions has not been determined. Thus, the objective of this study was to determine the role of M6P/IGF2R in regulation of cardiac myocyte growth and apoptosis. We down-regulated the expression of M6P/IGF2R in neonatal rat cardiac myocytes and examined the effect on cell proliferation and apoptosis. Infection of neonatal cardiomyocytes with an adenovirus expressing a ribozyme targeted against the M6P/IGF2R significantly reduced the level of M6P/IGF2R mRNA, as determined by RT-PCR and Ribonuclease Protection Assay (RPA). M6P-containing protein binding and endocytosis as well as the M6P/IGF2R-mediated internalization of 125I-IGF-II were lower in the ribozyme-treated cells than the control myocytes, indicating that the number of functional M6P/IGF2R in the ribozyme treated cells was reduced. Accordingly, a marked increase in cell proliferation and a reduced cell susceptibility to hypoxia- and TNF-induced apoptosis were observed in the ribozyme-treated cells. These findings suggest that M6P/IGF2R may play a role in regulation of cardiac myocyte growth and apoptosis. Down regulation of this gene in cardiac tissues might be a new approach to prevention of cell death or promotion of mitogenesis for certain heart diseases.
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DOI：
10.1006/clin.1995.1163
发表时间：
1995-12-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
CHAO, CC;HU, SX;PETERSON, PK
通讯作者：
PETERSON, PK
DOI：
10.1016/s0022-2828(86)80959-2
发表时间：
1986-08-01
影响因子：
5
作者：
RIDOUT, RM;WILDENTHAL, K;DECKER, RS
通讯作者：
DECKER, RS
DOI：
10.1073/pnas.88.2.580
发表时间：
1991-01-01
影响因子：
11.1
作者：
DENNIS, PA;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
2.6
作者：
Roberts, Lewis R.;Adjei, Philip N.;Gores, Gregory J.
通讯作者：
Gores, Gregory J.
影响因子：
--
作者：
Ellis, MJC;Leav, BA;Cullen, KJ
通讯作者：
Cullen, KJ