Details

Autor(en) / Beteiligte

• Zhang, Xi
• Guo, Jin-Ping
• Chi, Ya-Li
• Liu, Yan-Chun
• Zhang, Chuan-Sen
• Yang, Xiang-Qun
• Lin, Hai-Yan
• Jiang, Er- Peng
• Xiong, Shao-Hu
• Zhang, Zhi-Ying
• Liu, Bao-Hai

Titel

Endothelin-induced differentiation of Nkx[2.5.sup.+] cardiac progenitor cells into pacemaking cells

Ist Teil von

• Molecular and cellular biochemistry, 2012-07, Vol.366 (1-2), p.309

Ort / Verlag

Springer

Erscheinungsjahr

2012

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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, Nkx[2.5.sup.+] 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, Nkx[2.5.sup.+] 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, Nkx[2.5.sup.+] 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 Nkx[2.5.sup.+] CPCs differentiated into cardiac pacemaking cells after being treated with ET-1 and suggested that an ET1-Tbx3 molecular pathway govern/mediate this process. In conclusion, our study support the notion that pacemaking cells originate from Nkx[2.5.sup.+] CPCs present in embryonic heart tubes and endothelin-1 might be involved in diversification of cardiomyogenic progenitors toward the cells. Keywords Cardiac progenitor cell * Cardiac pacemaking cell * Embryonic heart tube * Cardiac development