Siddiqi Sailay, Gude Natalie, Hosoda Toru, Muraski John, Rubio Marta, Emmanuel Gregory, Fransioli Jenna, Vitale Serena, Parolin Carola, D'Amario Domenico, Schaefer Erik, Kajstura Jan, Leri Annarosa, Anversa Piero, Sussman Mark A
San Diego State University Heart Institute and Department of Biology, San Diego State University, CA 92182, USA.
Circ Res. 2008 Jul 3;103(1):89-97. doi: 10.1161/CIRCRESAHA.107.169334. Epub 2008 Jun 2.
Stem cell-specific proteins and regulatory pathways that determine self-renewal and differentiation have become of fundamental importance in understanding regenerative and reparative processes in the myocardium. One such regulatory protein, named nucleostemin, has been studied in the context of stem cells and several cancer cell lines, where expression is associated with proliferation and maintenance of a primitive cellular phenotype. We find nucleostemin is present in young myocardium and is also induced following cardiomyopathic injury. Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. Cardiac stem cells also express nucleostemin that is diminished in response to commitment to a differentiated phenotype. Overexpression of nucleostemin in cultured cardiac stem cells increases proliferation while preserving telomere length, providing a mechanistic basis for potential actions of nucleostemin in promotion of cell survival and proliferation as seen in other cell types.
决定自我更新和分化的干细胞特异性蛋白质及调控通路,对于理解心肌中的再生和修复过程已变得至关重要。一种名为核仁素的调控蛋白,已在干细胞及多种癌细胞系的背景下得到研究,其表达与原始细胞表型的增殖和维持相关。我们发现核仁素存在于年轻心肌中,并且在心肌病损伤后也会被诱导表达。心肌细胞中的核仁素表达由成纤维细胞生长因子 -2 诱导,并因Pim -1激酶活性而积累。心脏干细胞也表达核仁素,其表达会随着向分化表型的转变而减少。在培养的心脏干细胞中过表达核仁素会增加增殖,同时保持端粒长度,为核仁素在促进细胞存活和增殖方面的潜在作用提供了一个机制基础,这在其他细胞类型中也有体现。