Inositol polyphosphate-4-phosphatase type II(INPP4B)is a newly discovered PI(3,4,5)P3 phosphatase.Many studies have revealed that INPP4B is upregulated or downregulated in tumors of the digestive system,and the abnorm...Inositol polyphosphate-4-phosphatase type II(INPP4B)is a newly discovered PI(3,4,5)P3 phosphatase.Many studies have revealed that INPP4B is upregulated or downregulated in tumors of the digestive system,and the abnormal expression of INPP4B may be attributed to the occurrence,development,and prognosis of tumors of the digestive system.This paper reviews studies on the correlations between INPP4B and digestive system tumors and the roles of INPP4B in the development of different tumors to provide a theoretical basis for further research on its molecular mechanism and clinical application."INPP4B"and"tumor"were searched as key words in PubMed and in the CNKI series full text database retrieval system from January 2000 to August 2023.A total of 153 Englishlanguage studies and 30 Chinese-language studies were retrieved.The following enrollment criteria were applied:(1)Studies contained information on the biological structure and functions of INPP4B;(2)studies covered the influence of abnormal expression of INPP4B in digestive system tumors;and(3)studies covered the role of INPP4B in the diagnosis,treatment,and prognosis of digestive system tumors.After excluding the literature irrelevant to this study,61 papers were finally included in the analysis.INPP4B expression is low in gastric cancer,colon cancer,pancreatic cancer,and liver cancer but it has high expression in esophageal cancer,colon cancer,pancreatic cancer,and gallbladder cancer.INPP4B is involved in the occurrence and development of digestive system tumors through the regulation of gene expression and signal transduction.The abnormal expression of INPP4B plays an important role in the development of digestive system tumors.Studies on INPP4B provide new molecular insights for the diagnosis,treatment,and prognosis evaluation of digestive system tumors.展开更多
Diabetes is a complex metabolic disorder which can adversely affect reproductive function. SGK1 is found to be up-regulated in multiple tissues of diabetic patients. However, the effects of diabetes on endometrial SGK...Diabetes is a complex metabolic disorder which can adversely affect reproductive function. SGK1 is found to be up-regulated in multiple tissues of diabetic patients. However, the effects of diabetes on endometrial SGK1 expression and endometrial receptivity remain unknown. In this study, we established a streptozotocin-induced diabetic mouse model and observed reduced implantation sites, retarded development of pinopodes, increased SGK1, and aberrant expression of LIF and MUC1 in the endometrial epithelium. We injected the uterine lumen of normal mice with high-glucose solution and cultured endometrial cells in high-glucose medium to mimic intrauterine hyperglycemia. Both studies provided compelling evidence that hyperglycemia could lead to diminished embryo implantation and dysregulated SGK1, LIF and MUC1. Additionally, through over-expression of SGK1 in vivo and in vitro, we found that enhanced SGK1 also decreased LIF expression, increased MUC1 expression, and attenuated embryo implantation rate. We further identified that hyperglycemia-activated SMAD2/3 might be responsible for the enhancement of SGK1 and verified directly the interaction between SMAD3 and corresponding SMAD binding elements within SGK1 promoter. Taken together, our study confirmed the association between diabetes-related hyperglycemia and endometrial receptivity defects. Hyperglycemia-induced SGK1 has a tremendous role in this pathological process, rendering it as an attractive therapeutic target for diabetes-related reproductive disorders.展开更多
血清和糖皮质激素调节激酶1(serum and glucocorticoid-regulated kinase 1,SGK1)在神经系统激素释放、神经元兴奋和细胞增殖等生理过程中均发挥重要作用,SGK1也参与了中枢神经系统炎症及细胞凋亡等病理生理过程。越来越多的证据表明,S...血清和糖皮质激素调节激酶1(serum and glucocorticoid-regulated kinase 1,SGK1)在神经系统激素释放、神经元兴奋和细胞增殖等生理过程中均发挥重要作用,SGK1也参与了中枢神经系统炎症及细胞凋亡等病理生理过程。越来越多的证据表明,SGK1可能作为干预神经退行性疾病的关键性靶点。本文就SGK1在中枢神经系统功能调控中的作用及其分子机制的研究进展作一综述,并对最新发现的以SGK1为干预靶点的药物在中枢神经系统疾病中的潜力进行了讨论。展开更多
文摘Inositol polyphosphate-4-phosphatase type II(INPP4B)is a newly discovered PI(3,4,5)P3 phosphatase.Many studies have revealed that INPP4B is upregulated or downregulated in tumors of the digestive system,and the abnormal expression of INPP4B may be attributed to the occurrence,development,and prognosis of tumors of the digestive system.This paper reviews studies on the correlations between INPP4B and digestive system tumors and the roles of INPP4B in the development of different tumors to provide a theoretical basis for further research on its molecular mechanism and clinical application."INPP4B"and"tumor"were searched as key words in PubMed and in the CNKI series full text database retrieval system from January 2000 to August 2023.A total of 153 Englishlanguage studies and 30 Chinese-language studies were retrieved.The following enrollment criteria were applied:(1)Studies contained information on the biological structure and functions of INPP4B;(2)studies covered the influence of abnormal expression of INPP4B in digestive system tumors;and(3)studies covered the role of INPP4B in the diagnosis,treatment,and prognosis of digestive system tumors.After excluding the literature irrelevant to this study,61 papers were finally included in the analysis.INPP4B expression is low in gastric cancer,colon cancer,pancreatic cancer,and liver cancer but it has high expression in esophageal cancer,colon cancer,pancreatic cancer,and gallbladder cancer.INPP4B is involved in the occurrence and development of digestive system tumors through the regulation of gene expression and signal transduction.The abnormal expression of INPP4B plays an important role in the development of digestive system tumors.Studies on INPP4B provide new molecular insights for the diagnosis,treatment,and prognosis evaluation of digestive system tumors.
基金supported by the National Natural Science Foundation of China (81490742, 82001537)the Fundamental Research Funds for the Central Universities (2021FZZX003-02-18)the National Key Research and Development Program of China (2018YFC1004402)。
文摘Diabetes is a complex metabolic disorder which can adversely affect reproductive function. SGK1 is found to be up-regulated in multiple tissues of diabetic patients. However, the effects of diabetes on endometrial SGK1 expression and endometrial receptivity remain unknown. In this study, we established a streptozotocin-induced diabetic mouse model and observed reduced implantation sites, retarded development of pinopodes, increased SGK1, and aberrant expression of LIF and MUC1 in the endometrial epithelium. We injected the uterine lumen of normal mice with high-glucose solution and cultured endometrial cells in high-glucose medium to mimic intrauterine hyperglycemia. Both studies provided compelling evidence that hyperglycemia could lead to diminished embryo implantation and dysregulated SGK1, LIF and MUC1. Additionally, through over-expression of SGK1 in vivo and in vitro, we found that enhanced SGK1 also decreased LIF expression, increased MUC1 expression, and attenuated embryo implantation rate. We further identified that hyperglycemia-activated SMAD2/3 might be responsible for the enhancement of SGK1 and verified directly the interaction between SMAD3 and corresponding SMAD binding elements within SGK1 promoter. Taken together, our study confirmed the association between diabetes-related hyperglycemia and endometrial receptivity defects. Hyperglycemia-induced SGK1 has a tremendous role in this pathological process, rendering it as an attractive therapeutic target for diabetes-related reproductive disorders.
基金supported by the National Natural Science Foundation of China(No.82160688,31760290)Key Development Areas Project of Ganzhou Science and Technology(No.2022B-SF9554)the Innovation Team Foundation of Gannan Medical University(No.TD2021JC06)。
文摘血清和糖皮质激素调节激酶1(serum and glucocorticoid-regulated kinase 1,SGK1)在神经系统激素释放、神经元兴奋和细胞增殖等生理过程中均发挥重要作用,SGK1也参与了中枢神经系统炎症及细胞凋亡等病理生理过程。越来越多的证据表明,SGK1可能作为干预神经退行性疾病的关键性靶点。本文就SGK1在中枢神经系统功能调控中的作用及其分子机制的研究进展作一综述,并对最新发现的以SGK1为干预靶点的药物在中枢神经系统疾病中的潜力进行了讨论。
