Rubin Nicole, Darehzereshki Ali, Bellusci Saverio, Kaartinen Vesa, Ling Lien Ching
Heart Institute and Program of Developmental Biology and Regenerative Medicine, USA ; The Saban Research Institute of Children's Hospital Los Angeles, USA ; Department of Pathology, Keck School of Medicine, University of Southern California, USA.
Heart Institute and Program of Developmental Biology and Regenerative Medicine, USA ; The Saban Research Institute of Children's Hospital Los Angeles, USA.
J Cardiovasc Dis Diagn. 2013 Mar;1(1). doi: 10.4172/2329-9517.1000101.
Unlike zebrafish and newt hearts, mammalian hearts have limited capacity to regenerate. Upon injury or disease, the adult mammalian hearts form a fibrotic scar. Recently, it was shown that neonatal mouse hearts can regenerate similarly to adult zebrafish hearts. However, this capacity quickly decreases after postnatal day 7 (P7). Understanding the molecular mechanisms underlying neonatal heart regeneration might lead to therapeutic approaches for regenerating adult mammalian hearts. In this study, we utilized an inducible transgenic mouse model to determine the effects of FGF10 growth factor over expression on neonatal mouse heart regeneration/repair. Over expression of FGF10 in myocardium enhanced the expansion of Wt1 positive epicardial cells at 21 days after heart injury through increased proliferation. However, this expansion of epicardial cells did not lead to increased epithelial-to-mesenchymal transition or affect fibroblast formation or fibrosis, as seen by vimentin expression, after heart injury. Furthermore, neither continuous nor transient expression of FGF10 did not affect scar thickness or length after heart injury in neonatal hearts. Our results suggest that FGF10 can regulate epicardial cell expansion of neonatal mouse hearts after injury; however, FGF10 alone is not sufficient to cause beneficial effects on heart repair.
与斑马鱼和蝾螈的心脏不同，哺乳动物的心脏再生能力有限。在受到损伤或疾病影响时，成年哺乳动物的心脏会形成纤维化瘢痕。最近的研究表明，新生小鼠的心脏能够像成年斑马鱼的心脏一样进行再生。然而，这种能力在出生后第7天（P7）后会迅速下降。了解新生心脏再生的分子机制可能会为成年哺乳动物心脏的再生带来治疗方法。在本研究中，我们利用一种可诱导的转基因小鼠模型来确定FGF10生长因子过表达对新生小鼠心脏再生/修复的影响。心脏损伤后21天，心肌中FGF10的过表达通过增加增殖增强了Wt1阳性心外膜细胞的扩张。然而，如通过波形蛋白表达所见，心外膜细胞的这种扩张并未导致上皮-间充质转化增加，也未影响心脏损伤后成纤维细胞的形成或纤维化。此外，FGF10的持续表达或瞬时表达均未影响新生心脏损伤后的瘢痕厚度或长度。我们的结果表明，FGF10可以调节新生小鼠心脏损伤后的心外膜细胞扩张；然而，单独的FGF10不足以对心脏修复产生有益影响。
