Dynamic changes of Sonic Hedgehog signaling pathway in gastric mucosa of rats with MNNG‐induced gastric precancerous lesions

Abstract

Objective To explore the changes of Sonic Hedgehog (Shh) signaling pathway in the stomach mucosa during the formation of gastric precancerous lesions. Methods A total of 72 suckling rats in half genders were randomly and equally divided into the normal group and model group. The rats in the model group were administered with 0.1 ml 1‐methyl‐3‐nitro‐1‐nitrosoguanidine (MNNG) at the dosage of 800 mg/L for 10 days, whereas the rats in the normal group were similarly administered with normal saline. A total of 12 rats in each group were killed at the end of 10th, 22nd, and 34th weeks in half gender, respectively. Histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (HE) staining; the levels of Shh, Ptch1, Smo, Gli1, Gli2, Gli3, SuFu, Cyclin D1, Cyclin E1, c‐Myc, and β‐actin mRNAs in the gastric mucosa were determined by real‐time polymerase chain reaction; while the protein expression of Shh, Ptch1, Smo, Gli1, SuFu, Cyclin D1, Cyclin E1, c‐Myc, and p‐c‐Myc was detected by western blot analysis. Results With the development of atrophy and dysplasia of gastric mucosa, the levels of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and c‐Myc mRNAs increased, while those of Ptch1 and SuFu decreased. The expression of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and p‐c‐Myc proteins were elevated, while the expression of Ptch1 and SuFu proteins were decreased, however, without statistical difference. Conclusions Shh signaling is activated during the formation of gastric precancerous lesions, which indicates that the Shh signaling pathway participates in the development and progression of gastric precancerous lesions.

Gut Microbial Dysbiosis and Changes in Fecal Metabolic Phenotype in Precancerous Lesions of Gastric Cancer Induced With N-Methyl-N′-Nitro-N-Nitrosoguanidine, Sodium Salicylate, Ranitidine, and Irregular Diet

“…N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced mouse model, one of the chemical carcinogenesis models, has been widely used for the GC and development of gastric precancerous lesions ( Cai et al, 2018 , 2019 ; Xu et al, 2018 ; Zhang et al, 2018 ; Zhao et al, 2019 ). In this study, we modified the MNNG-induced model to combined with sodium salicylate drinking, ranitidine feed, and irregular diet (multifactor induction) that were used to simulate the main factors leading to chronic gastritis and GC such as irregular diet, gastric mucosal inflammation damage, and PPI abuse to establish PLGC rat model regarding our previous report ( Yu et al, 2020 ).…”

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

“…MNNG is typically used to construct a GPL animal model because it has the advantages of high stability and easy administration[ 11 ]. In this experiment, GPL was successfully induced in rats by a compound modeling method of drinking MNNG freely in the dark + 20% ethanol/hot saline-ranitidine by alternating gavage + alternating "satiation-starvation" (Figure 1A ).…”

Study on the Mechanism of Sancao Tiaowei Decoction in the Treatment of MNNG-Induced Precancerous Lesions of Gastric Carcinoma Through Hedgehog Signaling Pathway

“…The expressions of Shh, Smo, Gli-1, and Cyclin D1 mRNA in gastric mucosa increase in varying degrees. Smo activates downstream transcription factor Gli and initiates the transcription of many target genes ( 7 ). Knocking out the Smo gene, as a key signaling transduction molecule of the Hh signaling pathway, will block the Hh signaling pathway in rat embryos ( 26 ).…”

“…Currently, it’s generally believed that PLGC is irreversible and that the main purpose of the treatment is for the eradication of Helicobacter pylori , acid inhibition, the protection of the gastric mucosa, and symptomatic treatment ( 6 ), but the effect is not significant. Studies have shown that the hedgehog (Hh) signaling pathway in patients with PLGC is abnormally activated and has a specific expression in the process of the occurrence and development of PLGC ( 7 ).…”