Ni Bhraonain Emer, Turner Jack, Hannigan Karen, Sanders Kenton, Cobine Caroline
University of Nevada Reno.
Res Sq. 2024 Jun 11:rs.3.rs-4474290. doi: 10.21203/rs.3.rs-4474290/v1.
Interstitial cells of Cajal (ICC) and PDGFRα cells regulate smooth muscle motility in the gastrointestinal (GI) tract. However, their role(s) in esophageal motility are still unclear. The mouse esophagus has traditionally been described as almost entirely skeletal muscle in nature though ICC have been identified along its entire length. The current study evaluated the distribution of skeletal and smooth muscle within the esophagus using a mouse selectively expressing eGFP in smooth muscle cells (SMCs). The relationship of SMCs to ICC and PDGFRα cells was also examined. SMCs declined in density in the oral direction however SMCs represented ~ 25% of the area in the distal esophagus suggesting a likeness to the transition zone observed in humans. ANO1 intramuscular ICC (ICC-IM) were distributed along the length of the esophagus though like SMCs, declined proximally. ICC-IM were closely associated with SMCs but were also found in regions devoid of SMCs. Intramuscular and submucosal PDGFRα cells were densely distributed throughout the esophagus though only intramuscular PDGFRα cells within the LES and distal esophagus highly expressed SK3. ICC-IM and PDGFRα cells were closely associated with nNOS, VIP, VAChT and TH neurons throughout the LES and distal esophagus. GFAP cells resembling intramuscular enteric glia were observed within the muscle and were closely associated with ICC-IM and PDGFRα cells, occupying a similar location to c. These data suggest that the mouse esophagus is more similar to the human than thought previously and thus set the foundation for future functional and molecular studies using transgenic mice.
Cajal间质细胞（ICC）和血小板衍生生长因子受体α（PDGFRα）细胞调节胃肠道（GI）的平滑肌运动。然而，它们在食管运动中的作用仍不清楚。传统上，小鼠食管几乎完全被描述为骨骼肌性质，尽管在其全长都已鉴定出ICC。本研究使用在平滑肌细胞（SMC）中选择性表达eGFP的小鼠评估了食管内骨骼肌和平滑肌的分布。还研究了SMC与ICC和PDGFRα细胞的关系。SMC在口腔方向密度下降，然而SMC在食管远端占区域面积的约25%，提示与人类观察到的过渡区相似。ANO1肌内ICC（ICC-IM）沿食管全长分布，不过与SMC一样，在近端减少。ICC-IM与SMC密切相关，但也存在于没有SMC的区域。肌内和黏膜下PDGFRα细胞密集分布于整个食管，不过仅LES和食管远端的肌内PDGFRα细胞高表达SK3。在整个LES和食管远端，ICC-IM和PDGFRα细胞与nNOS、VIP、VAChT和TH神经元密切相关。在肌肉内观察到类似于肌内肠神经胶质细胞的GFAP细胞，它们与ICC-IM和PDGFRα细胞密切相关，占据与c相似的位置。这些数据表明，小鼠食管比之前认为的更类似于人类食管，从而为未来使用转基因小鼠进行功能和分子研究奠定了基础。
