Author:
Chen Ke,You Jingyi,Yang Shimin,Meng Xinyao,Chen Xuyong,Wu Luyao,Yu Xiaosi,Xiao Jun,Feng Jiexiong
Abstract
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.
Funder
Innovative Research Group Project of the National Natural Science Foundation of China
National Natural Science Foundation of China
Clinical Research Pilot Project of Tongji Hospital
Publisher
Springer Science and Business Media LLC
Subject
General Medicine,Surgery,Pediatrics, Perinatology and Child Health