College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, China.
Mol Cell Biochem. 2019 Jan;450(1-2):65-73. doi: 10.1007/s11010-018-3373-1. Epub 2018 May 28.
White adipose tissue (WAT) is the bulk of fatty tissues in humans. Enhancing the potential of WAT-derived stem cells (WATDCs) to generate cardiomyocytes may help supply sufficient number of therapeutically potent cells for heart repair in vivo. Therefore, we investigated whether ascorbic acid (AA) could facilitate the cardiac differentiation of WATDCs and the underlying mechanisms. Our results indicated that AA dose-dependently stimulates the cardiac differentiation of WATDCs, which is supported by the up-regulated expression of cardiac markers and the appearance of myotube-like cell morphologies. Time-course study showed that the front phase (0-4 days) is crucial for the action of AA on cardiac differentiation, which hints that AA may take effect through enhancing the proliferation of cardiac progenitor cells. EdU assay ascertained AA indeed promotes cell growth dose-dependently in the front phase. Further investigation indicated that AA induces the phosphorylation of MEK and ERK, and the synthesis of collagen I (Col I). Interference of MEK/ERK activity or Col I synthesis blocks the cardiomyogenic activity of AA in WATDCs. These findings demonstrated that AA facilitates WATDC cardiogenesis via promoting the proliferation of cardiac progenitor cells through MEK/ERK signaling and collagen synthesis.
白色脂肪组织（WAT）是人体中大量的脂肪组织。增强 WAT 来源的干细胞（WATDCs）生成心肌细胞的潜力可能有助于为体内心脏修复提供足够数量的治疗有效细胞。因此，我们研究了抗坏血酸（AA）是否可以促进 WATDC 的心脏分化及其潜在机制。我们的结果表明，AA 呈剂量依赖性地刺激 WATDC 的心脏分化，这得到了心脏标志物表达上调和肌管样细胞形态出现的支持。时程研究表明，前相（0-4 天）对于 AA 对心脏分化的作用至关重要，这暗示 AA 可能通过增强心脏祖细胞的增殖来发挥作用。EdU 测定证实 AA 在前相确实可以剂量依赖性地促进细胞生长。进一步的研究表明，AA 诱导 MEK 和 ERK 的磷酸化以及胶原 I（Col I）的合成。MEK/ERK 活性或 Col I 合成的干扰阻断了 AA 在 WATDC 中的心肌生成活性。这些发现表明，AA 通过 MEK/ERK 信号和胶原合成促进心脏祖细胞的增殖来促进 WATDC 的心脏发生。
