Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China.
Hubei Clinical Center of Hirschsprung Disease and Allied Disorders, Wuhan, China.
Pediatr Surg Int. 2023 Jun 6;39(1):214. doi: 10.1007/s00383-023-05479-x.
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?
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.
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.
Abnormally elevated expression of ACTA2 in the circular SM leads to hyperactive contraction, which may cause the spasm of aganglionic segments in HSCR.
α-平滑肌肌动蛋白 2（ACTA2）在肠平滑肌细胞（iSMCs）中表达，并与收缩性相关。先天性巨结肠（HSCR）是最常见的消化道畸形之一，表现为蠕动功能障碍和痉挛性平滑肌。无神经节细胞段的环形和纵向平滑肌（SM）排列紊乱。作为 iSMCs 的标志物，ACTA2 在无神经节细胞段是否表现出异常表达？ACTA2 的表达水平是否会影响 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？
采用免疫组织化学染色法检测 HSCR 患儿和 Ednrb 小鼠 iSMCs 中 ACTA2 的表达，采用小干扰 RNA（siRNA）敲低技术研究 Acta2 如何影响 iSMCs 的收缩功能。此外，还利用 Ednrb 小鼠研究 iSMCs ACTA2 在不同发育阶段的表达水平变化。
HSCR 患儿和 Ednrb 小鼠无神经节细胞段环形 SM 中 ACTA2 的表达高于正常对照组儿童和小鼠。下调 Acta2 可减弱肠平滑肌细胞的收缩能力。Ednrb 小鼠无神经节细胞段环形 SM 中 ACTA2 的表达从胚胎第 15.5 天（E15.5d）开始异常升高。
环形 SM 中 ACTA2 的异常升高导致过度活跃的收缩，这可能导致 HSCR 无神经节细胞段的痉挛。
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