Lidan Liu, Yanhui Peng, Wenping Liu, Jiajun Xu, Dali Li, Xiuwen Li
{"title":"gata结合蛋白4通过小核仁RNA宿主基因1/miR-361-3p轴促进Aβ1-42原纤维灌注大鼠的神经炎症和认知功能障碍。","authors":"Lidan Liu, Yanhui Peng, Wenping Liu, Jiajun Xu, Dali Li, Xiuwen Li","doi":"10.4103/cjop.CJOP-D-22-00057","DOIUrl":null,"url":null,"abstract":"<p><p>Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aβ<sub>1-42</sub> fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aβ<sub>1-42</sub> fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aβ<sub>1-42</sub> fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aβ<sub>1-42</sub> fibril-infused rats. Loss of GATA4 in Aβ<sub>1-42</sub> fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aβ<sub>1-42</sub> fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aβ<sub>1-42</sub> fibril-infused rats. In conclusion, silence of GATA4 ameliorated cognitive dysfunction and inhibited hippocampal inflammation and cell apoptosis through regulation of Sp1/SNHG1/miR-361-3p.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GATA-binding protein 4 promotes neuroinflammation and cognitive impairment in Aβ<sub>1-42</sub> fibril-infused rats through small nucleolar RNA host gene 1/miR-361-3p axis.\",\"authors\":\"Lidan Liu, Yanhui Peng, Wenping Liu, Jiajun Xu, Dali Li, Xiuwen Li\",\"doi\":\"10.4103/cjop.CJOP-D-22-00057\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aβ<sub>1-42</sub> fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aβ<sub>1-42</sub> fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aβ<sub>1-42</sub> fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aβ<sub>1-42</sub> fibril-infused rats. Loss of GATA4 in Aβ<sub>1-42</sub> fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aβ<sub>1-42</sub> fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aβ<sub>1-42</sub> fibril-infused rats. 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GATA-binding protein 4 promotes neuroinflammation and cognitive impairment in Aβ1-42 fibril-infused rats through small nucleolar RNA host gene 1/miR-361-3p axis.
Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aβ1-42 fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aβ1-42 fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aβ1-42 fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aβ1-42 fibril-infused rats. Loss of GATA4 in Aβ1-42 fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aβ1-42 fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aβ1-42 fibril-infused rats. In conclusion, silence of GATA4 ameliorated cognitive dysfunction and inhibited hippocampal inflammation and cell apoptosis through regulation of Sp1/SNHG1/miR-361-3p.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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