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Abstract：
BACKGROUND: Actin Alpha 2 (ACTA2) is expressed in intestinal smooth muscle cells (iSMCs) and is associated with contractility. Hirschsprung disease (HSCR), one of the most common digested tract malformations, shows peristaltic dysfunction and spasm smooth muscles. The arrangement of the circular and longitudinal smooth muscle (SM) of the aganglionic segments is disorganized. Does ACTA2, as a marker of iSMCs, exhibit abnormal expression in aganglionic segments? Does the ACTA2 expression level affect the contraction function of iSMCs? What are the spatiotemporal expression trends of ACTA2 during different developmental stages of the colon?
METHODS: Immunohistochemical staining was used to detect the expression of ACTA2 in iSMCs of children with HSCR and Ednrb-/- mice, and the small interfering RNAs (siRNAs) knockdown technique was employed to investigate how Acta2 affected the systolic function of iSMCs. Additionally, Ednrb-/- mice were used to explore the changes in the expression level of iSMCs ACTA2 at different developmental stages.
RESULTS: The expression of ACTA2 is higher in circular SM in the aganglionic segments of HSCR patients and Ednrb-/- mice than in normal control children and mice. Down regulation of Acta2 weakens the contraction ability of intestinal smooth muscle cells. Abnormally elevated expression of ACTA2 of circular smooth muscle occurs since embryonic day 15.5 (E15.5d) in aganglionic segments of Ednrb-/- mice.
CONCLUSIONS: Abnormally elevated expression of ACTA2 in the circular SM leads to hyperactive contraction, which may cause the spasm of aganglionic segments in HSCR.
METHODS: Immunohistochemical staining was used to detect the expression of ACTA2 in iSMCs of children with HSCR and Ednrb-/- mice, and the small interfering RNAs (siRNAs) knockdown technique was employed to investigate how Acta2 affected the systolic function of iSMCs. Additionally, Ednrb-/- mice were used to explore the changes in the expression level of iSMCs ACTA2 at different developmental stages.
RESULTS: The expression of ACTA2 is higher in circular SM in the aganglionic segments of HSCR patients and Ednrb-/- mice than in normal control children and mice. Down regulation of Acta2 weakens the contraction ability of intestinal smooth muscle cells. Abnormally elevated expression of ACTA2 of circular smooth muscle occurs since embryonic day 15.5 (E15.5d) in aganglionic segments of Ednrb-/- mice.
CONCLUSIONS: Abnormally elevated expression of ACTA2 in the circular SM leads to hyperactive contraction, which may cause the spasm of aganglionic segments in HSCR.
摘要：
背景：肌动蛋白α2（ACTA2）在肠平滑肌细胞（iSMC）中表达，并与收缩性相关。先天性巨结肠病（HSCR），最常见的消化道畸形之一,显示蠕动功能障碍和痉挛的平滑肌。神经节节段的圆形和纵向平滑肌（SM）的排列混乱。ACTA2作为iSMC的标志，ACTA2表达水平是否影响iSMCs的收缩功能？ACTA2在结肠不同发育阶段的时空表达趋势如何？
方法：免疫组化染色检测HSCR患儿和Ednrb-/-小鼠iSMCs中ACTA2的表达，并采用小干扰RNA（siRNA）敲低技术来研究Acta2如何影响iSMC的收缩功能。此外,用Ednrb-/-小鼠探讨不同发育阶段iSMCsACTA2表达水平的变化。
结果：在HSCR患者和Ednrb-/-小鼠的神经节节段中，环状SM中ACTA2的表达高于正常对照儿童和小鼠。Acta2的下调削弱了肠平滑肌细胞的收缩能力。自胚胎第15.5天（E15.5d）以来，Ednrb-/-小鼠的神经节节段中圆形平滑肌的ACTA2表达异常升高。
结论：环状SM中ACTA2表达异常升高导致过度活跃的收缩，这可能会导致HSCR中神经节节段的痉挛。
方法：免疫组化染色检测HSCR患儿和Ednrb-/-小鼠iSMCs中ACTA2的表达，并采用小干扰RNA（siRNA）敲低技术来研究Acta2如何影响iSMC的收缩功能。此外,用Ednrb-/-小鼠探讨不同发育阶段iSMCsACTA2表达水平的变化。
结果：在HSCR患者和Ednrb-/-小鼠的神经节节段中，环状SM中ACTA2的表达高于正常对照儿童和小鼠。Acta2的下调削弱了肠平滑肌细胞的收缩能力。自胚胎第15.5天（E15.5d）以来，Ednrb-/-小鼠的神经节节段中圆形平滑肌的ACTA2表达异常升高。
结论：环状SM中ACTA2表达异常升高导致过度活跃的收缩，这可能会导致HSCR中神经节节段的痉挛。
