Downregulation of P2Y2 and HuD during the development of the enteric nervous system in fetal rats with anorectal malformations

Abstract

Certain patients with anorectal malformations (ARMs) continue to suffer from postoperative dysphoria. The enteric nervous system (ENS) is closely associated with defecation. The purinergic receptor P2Y2 (P2Y2) and Hu antigen D (HuD) proteins contain multiple motifs that enable their activation and direct coupling to integrin and growth factor receptor signaling pathways; thus, they may serve as key points in ENS development. The aim of the present study was to investigate the expression pattern of P2Y2 and HuD proteins during anorectal development in ARM embryos. The embryogenesis of ARM in rats was induced by ethylenethiourea (ETU) on the 10th gestational day. The expression patterns of P2Y2 and HuD proteins were evaluated by immunohistochemistry and western blot analysis in normal, ETU and ARM rat embryos on embryonic days E17, E19 and E21; their mRNA levels were assessed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of the distal rectum of fetal rats. Immunohistochemistry of the distal rectum demonstrated that on E17, the expression levels of the two proteins were not different between the three groups. On E19, the expression of HuD was significantly decreased in the ARM group. On E21, the two proteins were significantly decreased in the ARM group. Additionally, the expression levels of the two proteins on E17 were significantly lower than on E21 in the ARM group. Western blotting and RT-qPCR also revealed that the P2Y2 and HuD proteins and mRNA expression levels were significantly decreased in the ARM groups when compared with the normal group on E17 and E21 (P<0.01). Thus, the present study demonstrated that downregulation of P2Y2 and HuD may partly be related to the development of the ENS in ARM embryos.

Global Development of Research on Anorectal Malformations over the Last Five Decades: A Bibliometric Analysis

“…China was the second most productive country on ARM research. Chinese studies reported frequently on basic ARM research including genetic pathways in animal models or the evolution of single-incision laparoscopic approaches to ARM [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. The high number of Japanese papers may be explained by the establishment of the Japanese Group for the Study of Anorectal Anomalies (JGSA) in 1974.…”

Prucalopride might improve intestinal motility by promoting the regeneration of the enteric nervous system in diabetic rats

“…Hud can promote the mitosis of neural stem cells, and it is an important protein involved in the differentiation and maturation of neurons (59). HuD is abundantly expressed in the healthy ENS and its expression is decreased in diseased tissues with loss of intestinal function (49).…”

Study on the correlation of high expression level of HuD with seborrheic keratosis and skin aging

“…Studies have shown that a high expression level of HuD is correlated with many diseases, especially aging diseases such as Alzheimer's disease and insulin insufficiency 8–10 . Meanwhile, scientists have found that a high expression level of HuD also plays an important role in the progression and metastasis of cancers such as oral squamous cell cancers, rectal cancer, and small cell lung cancer 11–13 . These findings reveal that HuD is related to organism aging, which is not only a marker to judge the prognosis of the disease, but also a potential target for treatment.…”

“…In addition, it has also been reported that HuD over‐expression plays a certain role in the progression and aggravation of some cancers, especially in oral squamous cell cancer, rectal cancer, and small cell lung cancer 11–13 …”

“…In addition, it has also been reported that HuD over-expression plays a certain role in the progression and aggravation of some cancers, especially in oral squamous cell cancer, rectal cancer, and small cell lung cancer. [11][12][13] Above studies have shown that HuD is related to some systemic diseases, especially in systemic aging diseases. Skin is the largest organ of human body, where there are neuroendocrine cells and Merkel cells, 14 which are located in the stratum basale of the epidermis.…”