Effects of activating transcription factor ATF4 on the development of intestinal inflammation in type 2 diabetes mellitus
Objective To explore the expression changes of activated transcription factor 4(ATF4)and its effect on the occurrence and development of intestinal inflammation in type 2 diabetes(T2D).Methods Streptozotocin(STZ)combined with high-fat diet was used to construct a mouse model of T2D.The protein expression level of ATF4 in intestinal tissues of mice was detected by Western Blot(WB)and immunohistochemistry(IHC).The pathological change of intestinal tissue was observed by hematoxylin-eosin(HE)staining.Real-time quantitative PCR(qRT-PCR)was used to detect the levels of inflammatory factors in the intestinal tissues of mice.Caco-2 cells were treated with high-concentration glucose medium to simulate the hyperglycemic state,and the protein expression level of ATF4 in the cells was detected by WB and immunofluorescence(IF).Caco-2 cells were transfected with ATF4 overexpression plasmid,and the protein expression level of ATF4 was detected by WB.The level of inflammatory was detected by qRT-PCR.Results Compared with normal mice,ATF4 protein expression in intestinal tissues of diabetic mice was significantly down-regulated,and the intestinal tissue showed significant pathologic changes,such as thinning of intestinal wall and sparse goblet cells.The levels of inflammatory factors in intestinal tissues of diabetic mice were significantly increased compared with those in normal mice,the difference is stootistically significant(P<0.05).Compared with normal group,the protein expression of ATF4 in Caco-2 cells was significantly down-regulated after high glucose treatment(P<0.05).The levels of inflammatory factors in Caco-2 cells were significantly increased compared with those in normal group.Overexpression of ATF4 reversed the expression levels of inflammatory factors in cells induced by high glucose environment(P<0.05).Conclusion Hyperglycemia may promote intestinal inflammatory response in T2D by inhibiting the expression of intestinal ATF4.
type 2 diabeteshyperglycemiaactivated transcription factor 4intestinal inflammation
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