The role of serum and glucocorticoid-induced kinase 1 （SGK1） pathway in the connective tissue growth factor （CTGF） expression was investigated in cultured human mesangial cells （HMCs） under high glucose. By usin...The role of serum and glucocorticoid-induced kinase 1 （SGK1） pathway in the connective tissue growth factor （CTGF） expression was investigated in cultured human mesangial cells （HMCs） under high glucose. By using RT-PCR and Western blot, the effect of SGK1 on the CTGF expression in HMCs under high glucose was examined. Overexpression of active SGK1 in HMCs transfected with PIRES2-EGFP- S422D hSGK1 （SD） could increase the expression of phosphorylated SGK1 and CTGF as compared with HMCs groups transfected with PIRES2-EGFP （FP） under high glucose or normal glucose. Overexpression of inactive SGK1 in HMCs transfected with PIRES2-EGFP- K127N hSGK1 （KN） could decrease phosphorylated SGK1 and CTGF expression as compared with HMCs groups transfected with FP under high glucose. In conclusion, these results suggest that high glucose-induced CTGF expression is mediated through the active SGK1 in HMCs.展开更多
The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulation ...The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulation by fluvastatin were also investigated. 24 male Wistar rats were randomly divided into normal control group （n = 8）, diabetic nephropathy group （n = 8） and fluvastatin-treated diabetic nephropathy group （15 mg/kg/d, n=8）. The metabolic parameters were measured at the 8th week. The expression of transforming growth factor β1 （TGF-β1） and fibronectin （FN） was immunohistochemically examined. The expression of SGK1 was detected by RT-PCR and Western blot, and CTGF mRNA was assessed by RT-PCR. As compared to DN, blood glucose, 24-h urinary protein, Cer and kidney weight index were all decreased and the weight was increased obviously in group F. At the same time, mesangial cells and extracellular matrix proliferation were relieved significantly. The levels of cortex SGK1 mRNA and protein were up-regulated, and both TGF-β1 and FN were down-regulated by fluvastatin. The mRNA of SGK1 was positively correlated with the CTGF, TGF-β1 and FN. SGK1 expression is markedly up-regulated in the renal cortex of DN group and plays an important role in the development and progress of diabetic nephropathy by means of signal transduction. Fluvastatin suppressed the increased SGKlmRNA expression in renal cortex and postponed the development of diabetic nephropathy.展开更多
Summary: To investigate the expression and the role of three isoforms of Serum and Glucocorticoid-inducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into...Summary: To investigate the expression and the role of three isoforms of Serum and Glucocorticoid-inducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24-h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.展开更多
目的构建含有小鼠血清和糖皮质激素诱导蛋白激酶3(serum and glucocorticoid-induced protein kinase 3,SGK3)基因的真核表达载体pcDNA3.1-MYC-SGK3-mCherry,并观察和验证其在转染细胞HEK293中的表达。方法通过聚合酶链式反应将实验室...目的构建含有小鼠血清和糖皮质激素诱导蛋白激酶3(serum and glucocorticoid-induced protein kinase 3,SGK3)基因的真核表达载体pcDNA3.1-MYC-SGK3-mCherry,并观察和验证其在转染细胞HEK293中的表达。方法通过聚合酶链式反应将实验室保存的真核表达质粒pcDNA3.1-MYC-SGK3中目的基因SGK3与mCherry融合并扩增出来,然后定向克隆至pcDNA3.1-MYC质粒中,经限制性内切酶消化和测序证实后,通过脂质体法转染HEK293细胞,Western blotting法检测目的基因的蛋白表达情况。结果测序结果与之前预期结果相符,证实pcDNA3.1-MYC-SGK3-mCherry真核表达载体构建成功。Western blotting结果显示,转染pcDNA3.1-MYC-SGK3-mCherry的HEK293细胞出现清晰的阳性反应条带,说明目的片段成功表达。结论pcDNA3.1-MYC-SGK3-mCherry真核表达载体构建成功。展开更多
BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN an...BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection.METHODS A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled.Immunohistochemistry was used to evaluate SGK3 expression.RESULTS SGK3 was overexpressed in 55(59.8%)patients with ESCN.SGK3 overexpression showed a significant correlation with death(P=0.031).Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group(P=0.013 and P=0.004,respectively).Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients(hazard ratio 4.729;95% confidence interval:1.042-21.458).CONCLUSION SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival.Thus,it might be a new prognostic factor for ESCN.展开更多
目的探讨右美托咪定调节血清磷脂酰肌醇-3-羟基酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(AKT)信号通路对老年全身麻醉患者术后认知功能的影响。方法选取2021年2月至2022年2月在荆门市第二人民医院行全麻手术的老年患者82例进行前瞻性研究,采用...目的探讨右美托咪定调节血清磷脂酰肌醇-3-羟基酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(AKT)信号通路对老年全身麻醉患者术后认知功能的影响。方法选取2021年2月至2022年2月在荆门市第二人民医院行全麻手术的老年患者82例进行前瞻性研究,采用抽签法将所有患者分为观察组和对照组,各41例。观察组在全身麻醉诱导开始10 min内静脉泵入右美托咪定,0.8μg/kg,随后以0.2~0.5μg·kg^(-1)·h^(-1)维持泵注;对照组静脉泵等量0.9%氯化钠溶液。观察并记录两组患者术前10 min、拔管前10 min、拔管后30 min的血流动力学指标;记录两组患者术中麻醉药用量及复苏情况。应用精神状态检查表(MMSE)记录患者术前、术后6 h、术后1 d、术后3 d MMSE评分,比较两组患者术前及术后即刻、术后1 d、术后3 d血清PI3K及AKT蛋白表达水平;通过Spearman秩相关分析检验PI3K、AKT与全身麻醉患者术后认知功能的相关性。结果与对照组比较,观察组拔管前10 min、拔管后30 min平均动脉压明显降低、心率明显减缓,差异均有统计学意义(P<0.05)。观察组术中使用丙泊酚及瑞芬太尼用量明显少于对照组,术后复苏各指标时间短于对照组,差异均有统计学意义(P<0.05)。观察组术后6 h MMSE评分低于术前,对照组术后6 h、术后1 d MMSE评分均低于术前,差异均有统计学意义(P<0.05);观察组术后6 h MMSE评分为(25.15±5.22)分,明显高于对照组[(21.57±3.58)分],差异有统计学意义(P<0.05)。术后即刻、术后1 d、术后3 d,两组PI3K、AKT水平均显著高于术前,观察组术后即刻、术后1 d、术后3 d PI3K、AKT水平均显著低于对照组,差异均有统计学意义(P<0.05)。经单因素相关分析,患者MMSE评分与血清PI3K、AKT水平呈负相关。结论右美托咪定可有效保护老年全身麻醉患者术后认知功能,其作用机制可能与PI3K/AKT信号通路有关。展开更多
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
基金a grant from the National Natural Sciences Foundation of China (No. 30600810)
文摘The role of serum and glucocorticoid-induced kinase 1 （SGK1） pathway in the connective tissue growth factor （CTGF） expression was investigated in cultured human mesangial cells （HMCs） under high glucose. By using RT-PCR and Western blot, the effect of SGK1 on the CTGF expression in HMCs under high glucose was examined. Overexpression of active SGK1 in HMCs transfected with PIRES2-EGFP- S422D hSGK1 （SD） could increase the expression of phosphorylated SGK1 and CTGF as compared with HMCs groups transfected with PIRES2-EGFP （FP） under high glucose or normal glucose. Overexpression of inactive SGK1 in HMCs transfected with PIRES2-EGFP- K127N hSGK1 （KN） could decrease phosphorylated SGK1 and CTGF expression as compared with HMCs groups transfected with FP under high glucose. In conclusion, these results suggest that high glucose-induced CTGF expression is mediated through the active SGK1 in HMCs.
文摘The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulation by fluvastatin were also investigated. 24 male Wistar rats were randomly divided into normal control group （n = 8）, diabetic nephropathy group （n = 8） and fluvastatin-treated diabetic nephropathy group （15 mg/kg/d, n=8）. The metabolic parameters were measured at the 8th week. The expression of transforming growth factor β1 （TGF-β1） and fibronectin （FN） was immunohistochemically examined. The expression of SGK1 was detected by RT-PCR and Western blot, and CTGF mRNA was assessed by RT-PCR. As compared to DN, blood glucose, 24-h urinary protein, Cer and kidney weight index were all decreased and the weight was increased obviously in group F. At the same time, mesangial cells and extracellular matrix proliferation were relieved significantly. The levels of cortex SGK1 mRNA and protein were up-regulated, and both TGF-β1 and FN were down-regulated by fluvastatin. The mRNA of SGK1 was positively correlated with the CTGF, TGF-β1 and FN. SGK1 expression is markedly up-regulated in the renal cortex of DN group and plays an important role in the development and progress of diabetic nephropathy by means of signal transduction. Fluvastatin suppressed the increased SGKlmRNA expression in renal cortex and postponed the development of diabetic nephropathy.
基金This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30270618).
文摘Summary: To investigate the expression and the role of three isoforms of Serum and Glucocorticoid-inducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24-h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.
文摘目的构建含有小鼠血清和糖皮质激素诱导蛋白激酶3(serum and glucocorticoid-induced protein kinase 3,SGK3)基因的真核表达载体pcDNA3.1-MYC-SGK3-mCherry,并观察和验证其在转染细胞HEK293中的表达。方法通过聚合酶链式反应将实验室保存的真核表达质粒pcDNA3.1-MYC-SGK3中目的基因SGK3与mCherry融合并扩增出来,然后定向克隆至pcDNA3.1-MYC质粒中,经限制性内切酶消化和测序证实后,通过脂质体法转染HEK293细胞,Western blotting法检测目的基因的蛋白表达情况。结果测序结果与之前预期结果相符,证实pcDNA3.1-MYC-SGK3-mCherry真核表达载体构建成功。Western blotting结果显示,转染pcDNA3.1-MYC-SGK3-mCherry的HEK293细胞出现清晰的阳性反应条带,说明目的片段成功表达。结论pcDNA3.1-MYC-SGK3-mCherry真核表达载体构建成功。
基金Supported by National Natural Science Foundation of China,No.82070682Beijing Municipal Science and Technology Commission,China,No.Z181100001718177.
文摘BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection.METHODS A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled.Immunohistochemistry was used to evaluate SGK3 expression.RESULTS SGK3 was overexpressed in 55(59.8%)patients with ESCN.SGK3 overexpression showed a significant correlation with death(P=0.031).Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group(P=0.013 and P=0.004,respectively).Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients(hazard ratio 4.729;95% confidence interval:1.042-21.458).CONCLUSION SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival.Thus,it might be a new prognostic factor for ESCN.
文摘目的探讨右美托咪定调节血清磷脂酰肌醇-3-羟基酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(AKT)信号通路对老年全身麻醉患者术后认知功能的影响。方法选取2021年2月至2022年2月在荆门市第二人民医院行全麻手术的老年患者82例进行前瞻性研究,采用抽签法将所有患者分为观察组和对照组,各41例。观察组在全身麻醉诱导开始10 min内静脉泵入右美托咪定,0.8μg/kg,随后以0.2~0.5μg·kg^(-1)·h^(-1)维持泵注;对照组静脉泵等量0.9%氯化钠溶液。观察并记录两组患者术前10 min、拔管前10 min、拔管后30 min的血流动力学指标;记录两组患者术中麻醉药用量及复苏情况。应用精神状态检查表(MMSE)记录患者术前、术后6 h、术后1 d、术后3 d MMSE评分,比较两组患者术前及术后即刻、术后1 d、术后3 d血清PI3K及AKT蛋白表达水平;通过Spearman秩相关分析检验PI3K、AKT与全身麻醉患者术后认知功能的相关性。结果与对照组比较,观察组拔管前10 min、拔管后30 min平均动脉压明显降低、心率明显减缓,差异均有统计学意义(P<0.05)。观察组术中使用丙泊酚及瑞芬太尼用量明显少于对照组,术后复苏各指标时间短于对照组,差异均有统计学意义(P<0.05)。观察组术后6 h MMSE评分低于术前,对照组术后6 h、术后1 d MMSE评分均低于术前,差异均有统计学意义(P<0.05);观察组术后6 h MMSE评分为(25.15±5.22)分,明显高于对照组[(21.57±3.58)分],差异有统计学意义(P<0.05)。术后即刻、术后1 d、术后3 d,两组PI3K、AKT水平均显著高于术前,观察组术后即刻、术后1 d、术后3 d PI3K、AKT水平均显著低于对照组,差异均有统计学意义(P<0.05)。经单因素相关分析,患者MMSE评分与血清PI3K、AKT水平呈负相关。结论右美托咪定可有效保护老年全身麻醉患者术后认知功能,其作用机制可能与PI3K/AKT信号通路有关。
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.
