Inhibition of Histone Deacetylase Expands the Renal Progenitor Cell Population
Inhibition of Histone Deacetylase Expands the Renal Progenitor Cell Population
复制标题
DOI：
10.1681/asn.2009080851
复制
发表时间：
2010-05-01
影响因子：
13.6
通讯作者：
Hukriede, Neil A.
中科院分区：
文献类型：
--
作者：
de Groh, Eric D.;Swanhart, Lisa M.;Hukriede, Neil A.
肾脏再生的首要标志之一是器官发生过程中通常所需的基因的重新激活。鉴定具有增强这种再激活潜力的化学物质可以在治疗上促进肾脏再生。在这里，我们发现 4-(苯硫基)丁酸 (PTBA) 扩大了斑马鱼肾脏器官发生分子标记的表达域。 PTBA 与组蛋白脱乙酰酶 (HDAC) 抑制剂 4-苯基丁酸和曲古抑菌素 A 具有结构和功能相似性；这些 HDAC 抑制剂的治疗也扩大了肾祖细胞群。体外和体内分析证实 PTBA 具有 HDAC 活性抑制剂的功能。此外，PTBA 介导的肾祖细胞扩增需要视黄酸信号传导。总之，这些结果支持肾祖细胞、HDAC 和类维生素A 通路之间的机制联系。 PTBA 是否有希望作为促进肾再生的治疗剂需要进一步研究。
One of the first hallmarks of kidney regeneration is the reactivation of genes normally required during organogenesis. Identification of chemicals with the potential to enhance this reactivation could therapeutically promote kidney regeneration. Here, we found that 4-(phenylthio)butanoic acid (PTBA) expanded the expression domains of molecular markers of kidney organogenesis in zebrafish. PTBA exhibits structural and functional similarity to the histone deacetylase (HDAC) inhibitors 4-phenylbutanoic acid and trichostatin A; treatment with these HDAC inhibitors also expanded the renal progenitor cell population. Analyses in vitro and in vivo confirmed that PTBA functions as an inhibitor of HDAC activity. Furthermore, PTBA-mediated renal progenitor cell expansion required retinoic acid signaling. In summary, these results support a mechanistic link among renal progenitor cells, HDAC, and the retinoid pathway. Whether PTBA holds promise as a therapeutic agent to promote renal regeneration requires further study.