Nestin expression is lost in ventricular fibroblasts during postnatal development of the rat heart and re-expressed in scar myofibroblasts
Nestin expression is lost in ventricular fibroblasts during postnatal development of the rat heart and re-expressed in scar myofibroblasts
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DOI：
10.1002/jcp.22794
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发表时间：
2012-02-01
影响因子：
5.6
通讯作者：
Calderone, Angelino
中科院分区：
文献类型：
--
作者：
Beguin, Pauline C.;Gosselin, Hugues;Calderone, Angelino
有研究报道，中间丝蛋白巢蛋白在发育过程中在各种非干/祖细胞中表达，在出生后生长过程中下调，并在损伤后重新表达。目前的研究验证了类似的模式在心室成纤维细胞中普遍存在的假设。在新生大鼠心脏中，巢蛋白水平明显高于成年心脏，分离的心脏细胞在心室成纤维细胞中选择性表达。在成人心室成纤维细胞中，巢蛋白表达明显低于新生儿心室成纤维细胞。在大鼠心脏缺血性损伤后，在瘢痕肌成纤维细胞亚群（37%）中检测到巢蛋白染色，免疫反应细胞的百分比高于成人心室成纤维细胞（7%），但显著低于新生儿心室成纤维细胞（86%）。此外，在成纤维细胞群体中观察到不同的3h -胸腺嘧啶摄取率，这可能部分与巢蛋白（+）细胞的不同百分比有关。为了评估巢蛋白在DNA合成中的作用，用含有shRNAmir的慢病毒感染新生儿心室成纤维细胞，该慢病毒直接针对中间丝蛋白。在没有凋亡反应的情况下，新生儿心室成纤维细胞中巢蛋白表达的部分缺失显著降低了基础DNA合成。因此，大鼠心脏的出生后发育与心室成纤维细胞巢蛋白表达的选择性丧失以及缺血损伤后肌成纤维细胞亚群的诱导有关。巢蛋白在瘢痕肌成纤维细胞中的重新表达可能是一种适应性反应，以提高其增殖速度并加速愈合过程。j .细胞。中国生物医学工程学报，2016,31(2):481 - 481。(C) 2011 Wiley期刊公司
Studies have reported that the intermediate filament protein nestin was expressed in various non-stem/progenitor cells during development, downregulated during postnatal growth and re-expressed following injury. The present study tested the hypothesis that an analogous paradigm was prevalent for ventricular fibroblasts. In the neonatal rat heart, nestin protein levels were significantly higher than the adult heart and the isolation of cardiac cells revealed a selective expression in ventricular fibroblasts. In adult ventricular fibroblasts, nestin protein expression was markedly lower compared to neonatal ventricular fibroblasts. Following ischemic damage to the rat heart, nestin staining was detected in a subpopulation of scar myofibroblasts (37%) and the percentage of immunoreactive cells was greater than adult ventricular fibroblasts (7%) but significantly lower than neonatal ventricular fibroblasts (86%). Moreover, dissimilar rates of 3H-thymidine uptake were observed among the fibroblast populations and may be related in part to the disparate percentage of nestin(+) cells. To assess the role of nestin in DNA synthesis, neonatal ventricular fibroblasts were infected with a lentivirus containing a shRNAmir directed against the intermediate filament protein. The partial depletion of nestin expression in neonatal ventricular fibroblasts significantly reduced basal DNA synthesis, in the absence of an apoptotic response. Thus, postnatal development of the rat heart was associated with a selective loss of nestin expression in ventricular fibroblasts and subsequent induction in a subpopulation of myofibroblasts following ischemic injury. The re-expression of nestin in scar myofibroblasts may represent an adaptive response to enhance their proliferative rate and accelerate the healing process. J. Cell. Physiol. 227: 813820, 2012. (C) 2011 Wiley Periodicals, Inc.