Endothelin-induced differentiation of Nkx2.5+ cardiac progenitor cells into pacemaking cells
| Autor: | Xi Zhang, Zhiying Zhang, Jinping Guo, Ya-Li Chi, Er-Peng Jiang, Xiang-Qun Yang, Bao-Hai Liu, Haiyan Lin, Chuansen Zhang, Shao-Hu Xiong, Yan-Chun Liu |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Potassium Channels Primary Cell Culture Clinical Biochemistry Action Potentials Down-Regulation Biology Connexins Rats Sprague-Dawley Transcription (biology) Internal medicine Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels medicine Animals Gene silencing Progenitor cell Molecular Biology Gene Cells Cultured Sinoatrial Node Homeodomain Proteins Endothelin-1 Embryonic heart Stem Cells Cell Differentiation Cell Biology General Medicine Transfection Myocardial Contraction Rats Cell biology Endocrinology Homeobox Protein Nkx-2.5 cardiovascular system Electrical conduction system of the heart T-Box Domain Proteins Endothelin receptor Transcription Factors |
| Zdroj: | Molecular and Cellular Biochemistry. 366:309-318 |
| ISSN: | 1573-4919 0300-8177 |
| DOI: | 10.1007/s11010-012-1309-8 |
| Popis: | The mechanisms governing the development of cardiac pacemaking and conduction system are not well understood. In order to provide evidence for the derivation of pacemaking cells and the signal that induce and maintain the cells in the developing heart, Nkx2.5(+) cardiac progenitor cells (CPCs) were isolated from embryonic heart tubes of rats. Endothelin-1 was subsequently added to the CPCs to induce differentiation of them towards cardiac pacemaking cells. After the treatment, Nkx2.5(+) CPCs displayed spontaneous beating and spontaneously electrical activity as what we have previously described. Furthermore, RT-PCR and immunofluorescence staining demonstrated that Tbx3 expression was increased and Nkx2.5 expression was decreased in the induced cells 4 days after ET-1 treatment. And the significantly increased expression of Hcn4 and connexin-45 were detected in the induced cells 10 days after the treatment. In addition, Nkx2.5(+) CPCs were transfected with pGCsi-Tbx3 4 days after ET-1 treatment in an attempt to determine the transcription regulatory factor governing the differentiation of the cells into cardiac pacemaking cells. The results showed that silencing of Tbx3 decreased the pacemaking activity and led to down-regulation of pacemaker genes in the induced cells. These results confirmed that Nkx2.5(+) CPCs differentiated into cardiac pacemaking cells after being treated with ET-1 and suggested that an ET-1-Tbx3 molecular pathway govern/mediate this process. In conclusion, our study support the notion that pacemaking cells originate from Nkx2.5(+) CPCs present in embryonic heart tubes and endothelin-1 might be involved in diversification of cardiomyogenic progenitors toward the cells. |
| Databáze: | OpenAIRE |
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