Dynamic Expression of HIF-1α/Sonic Hedgehog Signaling Pathway in the Evolution of Gastric Mucosal Lesions
QIAN Suting1, YU Jianshun2, QIU Jing1, CHEN Zhiyun3, LIU Qingsheng4*
This paper aimed to study the relationship between the dynamic expression of HIF-1α/Sonic Hedgehog (Shh) signaling pathway and the evolution of gastric mucosal lesions. 72 rats (SD rats, 8+weeks of age, male) were randomly divided into normal group and model group. After establishing model of precancerous lesions with MNNG (N-methyl-N’-nitro-N-nitrosoguanidine), six rats in the two groups were killed respectively at the end of the 4th, 10th, 16th, 22nd, 28th and 34th week. The pathological changes of gastric mucosa were detected by HE (Hematoxylin-eosin) staining. The mRNA expressions of HIF-1α, VEGF, CTGF, iNOS, ET-1, Shh, Ptch1, Smo, SuFu, Gli1, CYC-D1, CYC-E1, and C-MYC were detected by qRT-PCR. The proteins expressions of HIF-1α, CTGF, iNOS, ET-1/2/3, Shh, Ptch1, Smo, SuFu, Gli1, CYC-D1, and P-C-MyC were detected by Western blot. The results showed that HE staining showed the gastric mucosa of the rats in the model group occurred inflammation, atrophy, intestinal meterosis, and even heterosis. From 28th weeks, the model group rats gastric mucosa tissues HIF-1α, VEGF, CTGF, iNOS, ET-1, Shh, Smo, Gli1, Cyc-D1, Cyc-E1 mRNA expression had varying degrees of growth. At 34 weeks differences between the two groups was statistically significant (P<0.05). SuFu mRNA expression showed a slightly decreasing trend with the increase of time, and the difference was statistically significant at the 34th week (P<0.05). Ptch1 mRNA expression showed a decreasing trend except for the 16th week, but the difference was not statistically significant (P>0.05). The protein expression of HIF-1α, CTGF, iNOS, ET-1/2/3, Gli-1 in the model group showed an increasing trend, and the difference between groups had statistical significance from 28 weeks (P<0.05). There were no significant differences in the protein expression of Shh, Smo and SUFU (P>0.05). The protein expression of Ptch1 showed a slightly decreasing trend, and the difference was statistically significant at the 4th week (P<0.05). The protein expression of Gli-1 showed a downward trend, and the difference was statistically significant at the 16th week (P<0.05). The protein expression of Cyc-D1 decreased at the 16th week, and the difference had statistical significance (P<0.05). The protein expression of P-c-Myc showed an upward trend, and the difference was statistically significant at the 10th week (P<0.05). These results suggest that HIF-1α/Shh signaling pathway is involved in the process of gastric mucosal malignant lesions, whose key genes may serve as important targets to delay or inhibit gastric mucosal lesions.
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