ABSTRACT
Objective@#To analyze the biological network regulation and key proteins of gene expression microarray in human normal prostate epithelial cells after treated with low-dose cadmium, and provide some new theoretical evidence for the pathogenesis of cadmium-related prostate cancer.@*METHODS@#We downloaded 19 copies of gene chip data from the Gene Expression Omnibus (GEO), involving 9 samples of prostate epithelial cells exposed to low-dose cadmium and 10 cases of normal control. Using the Gene-Cloud of Biotechnology Informs platform, GenClip2.0 and Sytoscape 3.5.1, we screened differentially expressed genes, explored their protein interaction networks and biological pathways and, from the perspective of transcriptome, analyzed the changes in the genetic network of normal human prostate epithelial cells and their possible molecular biological functions after low-dose cadmium treatment.@*RESULTS@#Totally, 1 050 (1.92%) differentially expressed genes were found in the prostate epithelial cells treated with low-dose cadmium, involved in such biological functions as the cell physiological process, MAPK regulation, regulation of intracellular signal transduction, and immunological effect. The HSP90AB1, BUB3 and PRKAR1A genes were the core nodes of the protein network, which showed statistically significant differences in their expressions and a correlation with the malignant transformation of normal cells.@*CONCLUSIONS@#Low-dose cadmium can cause genetic changes in normal human prostate epithelial cells and the differentially expressed genes are mainly involved in such biological functions as the cell physiological process, MAPK regulation, regulation of intracellular signal transduction, and immunological effect.
ABSTRACT
AIM:To explore the effect of sex on the formation of chronic pancreatitis(CP)by comparing the differences in L-arginine-induced CP model between male and female mice.METHODS:Male(n=42)and female(n=42)Kunming mice were randomly divided into 4 groups:female control group, female CP group, male control group and male CP group(n=18 in each control group, n =6 at each time point; n=24 in each CP group, n=8 at each time point).The mice in CP groups were intraperitoneally injected with 20%L-arginine(3 g/kg,twice/d,1 d/week).After modeling for 2 weeks,4 weeks and 6 weeks,the mice were anesthetized and sacrificed.The morphological changes and the degree of fibrosis in the pancreas were observed by HE and Masson staining.The positive expression rate of F4/80 in the pancreatic tissues was observed by the method of immunohistochemistry.The mRNA expression of interleukin-6(IL-6), α-smooth muscle actin(α-SMA)and fibronectin(FN)in the pancreas were detected by real-time PCR.The protein of pancreas was extracted to detect the expression of α-SMA and FN by Western blot.RESULTS:At 2 weeks,4 weeks and 6 weeks after intraperitoneal injection of L-arginine, the pancreatic tissues were obviously injured and exhibited different degrees of fibrosis in female and male CP groups.At the same time,there were significant differences in the degree of pan-creatic injury between male and female mice,and the degree of pancreatic lesion in the male mice was significantly more severe.The positive rate of F4/80 in the pancreas of male CP mice was significantly higher than that in female CP group at the same time point after modeling.At every time point, the mRNA expression of IL-6 in the pancreas was increased in both female and male CP groups,but that in male CP group was higher(P<0.05).The fibrosis indexes,α-SMA and FN, were both highly expressed at mRNA and protein levels after modeling, but compared with the female group, the time of positive expression in male mice was earlier and the expression level was higher(P<0.05).CONCLUSION: The CP model is successfully established by intraperitoneal injection of 20%L-arginine,and a difference in the degree of pathologic alteration in pancreas between male and female mice exists.CP is more effectively induced by L-arginine in male mice,and the degree of fibrosis is more pronounced.The reason may be related to the sensitivity of male mice to L-arginine,causing more serious inflammatory response.Therefore,male mice are more suitable for establishing CP animal model.