No association of G-protein beta polypeptide 3 polymorphism with irritable bowel syndrome: Evidence from a meta-analysis

AIM:To clarify the associations between G-protein beta polypeptide 3(GNB3)C825T polymorphism and risk of the irritable bowel syndrome(IBS)by a meta-analysis.METHODS:We searched relevant studies in PubMed,EMBASE,CNKI,Google Scholar,Ovid and Cochrane library prior to October 2013.The strengths of the associations between GNB3 C825T polymorphism and IBS risk were estimated by odds ratios(ORs)with 95%confidence interval(CIs).RESULTS:We identified seven case-control studies with 1085 IBS cases and 1695 controls for the analysis.We found no significantly associations of GNB3 C825T polymorphism with IBS risk in the overall population(CC vs TT,OR=1.12,95%CI:0.86-1.45;CC+CT vs TT,OR=1.17,95%CI:0.92-1.49;TT+CT vs CC,OR=0.93,95%CI:0.80-1.08;C vs T,OR=1.08,95%CI:0.97-1.21).Subgroup analysis did not reveal significant associations either in Asian population or Caucasian population.The pooled results of four studies fail to show associations of GNB3 C825T polymorphism with subtypes of IBS(constipation-dominant type,diarrheadominant type and mixed type).CONCLUSION:The present study suggests no associations of GNB3 C825T polymorphism with IBS risk.

MicroRNA-760 acts as a tumor suppressor in gastric cancer development via inhibiting G-protein-coupled receptor kinase interacting protein-1 transcription

BACKGROUND Gastric cancer(GC)has become a serious threat to people's health.Accumulative evidence reveals that dysregulation of numerous microRNAs(miRNAs)has been found during malignant formation.So far,the role of microRNA-760(miR-760)in the development of GC is largely unknown.AIM To measure the expression level of miR-760 in GC and investigate its role in gastric tumorigenesis.METHODS Real-time quantitative polymerase chain reaction and Western blot analysis were used to measure the expression of miR-760 and G-protein-coupled receptor kinase interacting protein-1(GIT1).Cell growth was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)and cell colony formation assays.Apoptosis was assessed by flow cytometric analysis.The relationship between miR-760 and GIT1 was verified by luciferase reporter assay.RESULTS The results showed that the expression of miR-760 was decreased in GC and associated with poor clinical outcomes in GC patients.Furthermore,miR-760 restrained cell proliferation and cell colony formation and induced apoptosis in GC cells.In addition,miR-760 directly targeted GIT1 and negatively regulated its expression in GC.GIT1 was upregulated in GC and predicted a worse prognosis in GC patients.We also found that upregulation of GIT1 weakened the inhibitory CONCLUSION In conclusion,miR-760 targets GIT1 to inhibit cell growth and promote apoptosis in GC cells.Our data demonstrate that miR-760 may be a potential target for the treatment of GC.

G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease

Coronary heart disease(CHD) continues to be the greatest mortality risk factor in the developed world. Estrogens are recognized to have great therapeutic potential to treat CHD and other cardiovascular diseases; however,a significant array of potentially debilitating side effects continues to limit their use. Moreover,recent clinical trials have indicated that long-term postmenopausal estrogen therapy may actually be detrimental to cardiovascular health. An exciting new development is the finding that the more recently discovered G-protein-coupled estrogen receptor(GPER) is expressed in coronary arteries-both in coronary endothelium and in smooth muscle within the vascular wall. Accumulating evidence indicates that GPER activation dilates coronary arteries and can also inhibit the prolif-eration and migration of coronary smooth muscle cells. Thus,selective GPER activation has the potential to increase coronary blood flow and possibly limit the debilitating consequences of coronary atherosclerotic disease. This review will highlight what is currently known regarding the impact of GPER activation on coronary arteries and the potential signaling mechanisms stimulated by GPER agonists in these vessels. A thorough understanding of GPER function in coronary arteries may promote the development of new therapies that would help alleviate CHD,while limiting the potentially dangerous side effects of estrogen therapy.

Isoleucine, an Essential Amino Acid, Induces the Expression of Human <i>β</i>Defensin 2 through the Activation of the G-Protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia

Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.

Genetic predisposition to essential hypertension in a Mongolian population Detecting the C825T polymorphism of the G-protein beta 3 subunit gene

BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful for prevention to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between C825T polymorphisms of G-protein beta 3 subunit gene （GNB3）, the important candidate gene of various disease of cardiovascular system, and Mongolian patients with essential hypertension. DESIGN： A comparative observation. SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： Totally 267 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia. The patients were screened based on the diagnostic standard of hypertension set by WHO in 1999, and the enrolled subjects were divided into two groups according to the level of blood pressure： ① Normal blood pressure group （n =124）： 64 males and 60 females, systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg=0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg;②Essential hypertension group （n =143）： 71 males and 72 females, including 60 patients with simple high SBP （SBP ranged 145 to 195 mm Hg, whereas DBP 〈 90 mm Hg）. METHODS： Peripheral venous blood （5 mL） was drawn from all the subjects, the genome DNA was extracted, and the polymorphisms of the GNB3 C825T genotype were detected with the Sequenom system. Polyrnerase chain reaction （PCR） experiment and SNP detection were performed in Beijing Huada gene laboratory. Then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CI） were calculated. MAIN OUTCOME MEASURES： The distributions of GNB3 C825T genotypes and alleles were observed. RESULTS： All the 267 Mongolian subjects were involved in the analysis of results.① GNB3 C825T genotypes： In Mongolian population, the frequencies of CC, CT and TT genotypes at GNB3 C825T site in the essential hypertension group （48%, 41%, 11%） were not obvious different from those in the normal blood pressure group （43%, 47%, 10%, x^2 =0.162, P =0.688; OR：1.176, 95%CI： 0.533- 2.592）, whereas there were also no obvious differences between the simple high SBP group （57%, 35%, 8%） and the normal blood pressure group （x^2 =0.733, P =0.392; OR：1.957, 95%CI： 0.623- 6.143）. ②GNB3 C825T alleles： In Mongolian population, The frequencies of C and T alleles in the essential hypertension group （69%, 31%） were not obviously different from those in the normal blood pressure group （67%, 33%, x^2 =0.094, P = 0.759; OR：0.945, 95%CI：0.657 - 1.358）, whereas there were also no obvious differences between the simple high SBP group （74%, 26%） and the normal blood pressure group （ x^2 =2.133, P =0.144; OR：0.697, 95%CI： 0.428- 1.133）. CONCLUSION： GNB3 C825T site may be not a genetic marker of essential hypertension and simple high SBP in Mongolian population.

New insights into sodium transport regulation in the distal nephron:Role of G-protein coupled receptors

The renal handling of Na^+ balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part(i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na^+ excretion and are the target of many different regulatory processes that modulate Na^+ retention more or less efficiently. G-protein coupled receptors(GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na^+ absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na^+ excretion, this review also highlights the complexity of these different pathways, and the connections between them.

G-protein coupled receptors and synaptic plasticity in sleep deprivation

Insufficient sleep has been correlated to many physiological and psychoneurological disorders.Over the years,our understanding of the state of sleep has transcended from an inactive period of rest to a more active state involving important cellular and molecular processes.In addition,during sleep,electrophysiological changes also occur in pathways in specific regions of the mammalian central nervous system(CNS).Activity mediated synaptic plasticity in the CNS can lead to long-term and sometimes permanent strengthening and/or weakening synaptic strength affecting neuronal network behaviour.Memory consolidation and learning that take place during sleep cycles,can be affected by changes in synaptic plasticity during sleep disturbances.G-protein coupled receptors(GPCRs),with their versatile structural and functional attributes,can regulate synaptic plasticity in CNS and hence,may be potentially affected in sleep deprived conditions.In this review,we aim to discuss important functional changes that can take place in the CNS during sleep and sleep deprivation and how changes in GPCRs can lead to potential problems with therapeutics with pharmacological interventions.

Desensitization of G-protein-coupled receptors induces vascular hypocontractility in response to norepinephrine in the mesenteric arteries of cirrhotic patients and rats

BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

Pathogenicity Assay for <i>Cochliobolus heterostrophus</i>G-Protein and MAPK Signaling Deficiency Strains

Cochliobolus heterostrophus is an agriculturally important and emerging model pathogen for studying the signaling hierarchies' role during the maize host colonization. In particular, G-protein and MAPK-linked pathways are playing a major role during pathogenesis. Although gene disruption studies are an efficient way of identifying the role of these cascades, differentiating between the mutant strains’ virulence ability may become an intricate task. For example, in C. heterostrophus, mutants in a G-protein α subunit gene, cga1, are defective in mating and appressorium formation, but unlike mutants in homologous genes in other fungal pathogens, the cga1 mutants remained highly virulent to corn under some host physiological conditions. Here, we used the cga1 strain as a model for developing an in vivo sensitive and accurate pathogenicity assay. A detailed and well controlled analysis of wild type (WT) and cga1 pathogenic behavior revealed that detached leaves are significantly more vulnerable to the disease than intact ones. In intact leaves, cga1 mutants were less infective of maize under most conditions. This difference was maximized when the first seedling leaf was chosen for inoculation and when the infected leaves, with spores or mycelia fragments droplets, were incubated for a period of four days. This optimal condition set enabled us to classify the C. heterostrophus G-protein signaling mutants deficient in α, β or both subunits in order of decreasing virulence: WT > cga1> cgb1> cga1 cgb1. The method presented proved to be accurate and sensitive enough to identify even slight variations in virulence. Moreover, it could be modified for use in studies of other foliar phytoparasitic fungi.

Association between G-protein β3 subunit gene and isolated systolic blood pressure elevation of greater than 130 mmHg: A large-scale cross-sectional study in the Japanese population

AIM To investigate whether GNB3 C825 T single nucleotide polymorphism(SNP) contributes to systolic blood pressure(SBP) ≥ 130 mmH g in a large-scale cross-sectional study among the Japanese population with diastolic blood pressure(DBP) < 85 mmH g. METHODS We analyzed 11008 Japanese subjects, including 2797 cases(SBP ≥ 130 and DBP < 85 mmH g) who were not taking anti-hypertensive medication and 8211 controls(SBP < 130 and DBP < 85 mmH g), all of whom enrolled in the genome banking project of the 21 st Century COE(Center of Excellence) Program at Jichi Medical University. Subjects were divided into four groups according to gender(male and female) and age(≤ 49 years and ≥ 50 years). GNB3 gene polymorphism was determined using the TaqM an probe method. We compared the frequencies of alleles and genotypes between cases and controls by chi-squared test. The strength of the associations was estimated by odds ratios(ORs) and 95%CI by using logistic regression analysis. The ORs were adjusted for age and body mass index. RESULTS Allele and genotype distributions significantly differed between cases and controls only in males aged ≤ 49 years. Compared to the CC genotype, a significant OR was obtained in the TT genotype among males aged ≤ 49 years.CONCLUSION This study indicates that the TT genotype of the GNB3 C825 T SNP may contribute to SBP elevation of greater than 130 mmH g compared to the CC genotype in Japanese males aged ≤ 49 years.

G-protein β subunit AGB1 positively regulates salt stress tolerance in Arabidopsis

The heterotrimeric GTP-binding proteins（G-proteins） in eukaryotes consisted of α, β and γ subunits and are important in molecular signaling by interacting with G-protein-coupled receptors（GPCR）, on which to transduce signaling into the cytoplast through appropriate downstream effectors. However, downstream effectors regulated by the G-proteins in plants are currently not well defined. In this study, the transcripts of AGB1, a G protein β subunit gene in Arabidopsis were found to be down-regulated by cold and heat, but up-regulated by high salt stress treatment. AGB1 mutant（agb1-2） was more sensitive to high salt stress than wild-type（WT）. Compared with WT, the cotyledon greening rates, fresh weight, root length, seedling germination rates and survival rates decreased more rapidly in agb1-2 along with increasing concentrations of Na Cl in normal（MS） medium. Physiological characteristic analysis showed that compared to WT, the contents of chlorophyll, relative proline accumulation and peroxidase（POD） were reduced, whereas the malonaldehyde（MDA） content and concentration ratio of Na＋/K＋ were increased in agb1-2 under salt stress condition. Further studies on the expression of several stress inducible genes associated with above physiological processes were investigated, and the results revealed that the expressions of genes related to proline biosynthesis, oxidative stress response, Na＋ homeostasis, stress- and ABAresponses were lower in agb1-2 than in WT, suggesting that those genes are possible downstream genes of AGB1 and that their changed expression plays an important role in determining phenotypic and physiologic traits in agb1-2. Taken together, these findings indicate that AGB1 positively regulates salt tolerance in Arabidopsis through its modulation of genes transcription related to proline biosynthesis, oxidative stress, ion homeostasis, stress- and ABA-responses.

G-protein beta 3 subunit polymorphisms and essential hypertension： a case-control association study in northern Han Chinese

ObjectiveTo 探索在三多型性之间的协会[ C825T ， C1429T 和 G (编码 3 子单元( GNB3 )和由执行盒子控制的高血压在北汉中国 population.MethodsWe 学习的 G 蛋白质贝它的基因的-350)A]招募了 731 个高血压的病人和 673 个控制题目(计算力量价值是 &#x0003e ；0.8 ) 。Genotyping 被执行识别 C825T， C1429T 和 G (用 TaqMan 试金的 -350)A 多型性。比较突变而产生之遗传并且在盒子和控制之间的 genotypic 频率被使用 chi 平方测试做。逻辑回归分析被执行在不同基因模型下面调查在 GNB3 基因的三多型性之间的关系(添加剂，主导、后退的模型) C825T ， C1429T 和 G 的 .ResultsThe 遗传型分发和等位基因频率( -350)A 多型性没在高血压的病人和控制题目之间显著地不同，当完整的样品被估计时或当样品被性成层时。没有重要协会在 C825T， C1429T 和 G 之间被观察(-350)A 多型性和在任何基因模型的必要高血压的风险。连接不平衡仅仅在 C825T 和 C1429T 多型性之间被检测。Haplotype 分析没 hypertension.ConclusionsOur 学习的风险建议了的显著地增加的三估计的 haplotypes 观察那任何一个 GNB3 基因多型性[C825T， C1429T 和 G (-350)A] 显著地没用北汉汉语与必要高血压被联系人口。

Heterotrimeric G-protein is involved in phytochrome A-mediated cell death of Arabidopsis hypocotyls

heterotrimeric guanine 核苷酸绑定蛋白质(G 蛋白质) 被表明了各种各样的发信号调停在植物的小径。然而，它在发信号的 phytochrome A (phyA ) 的角色留下逃犯。在这研究，我们发现新调停 phyA 的显型指明了 far-red 照耀(FR ) preconditioned 房间死亡，它仅仅在跟随暴露到白光(WL ) 的 FR-grown 幼苗的胚轴发生。房间死亡在 G 变异的 gpa1 被减轻，但是与野类型(WT ) 比较在 G 变异的 agb1 加重了，在调停 phyA 的房间死亡小径的 GPA1 和 AGB1 的对抗角色的陈述语气。进一步的调查显示 nonphotoconvertible protochlorophyllide (Pchlide633 ) 的导致 FR 的累积，在暴露上产生反应的氧种类(ROS ) 到 WL，为前提 FR 的房间死亡被要求。而且， ROS 主要在叶绿体被检测用荧光灯探查。有趣地，到黑暗成年的幼苗的 H2O2 的申请导致类似于前提 FR 的房间死亡的显型。这表明 ROS 是为房间死亡的一个批评调停人。另外，我们观察到 agb1 比 WT 幼苗对 H2O2 更敏感，显示 G 蛋白质可以也修改到 ROS 应力的幼苗的敏感。一起拿这些结果，我们推断 G 蛋白质可以涉及表明小径调整 Arabidopsis 胚轴的前提 FR 的房间死亡的 phyA。在 phyA 位于 G 蛋白质的参与下面发信号的可能的机制在这研究被讨论。

Mechanisms of regulation and function of G-protein-coupled receptor kinases

G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated form of G-protein-coupled receptor (GPCR) to affect receptor phosphorylation and to initiate profound impairment of receptor signaling, or desensitization. GPCR forms the largest family of cell surface receptors, and defects in GRK function have the potential consequence to affect GPCR-stimulated biological responses in many pathological situations.

利用CRISPR/Cas9构建敲除小鼠模型研究PPP2R3A基因对心脏功能的影响

目的 应用CRISPR/Cas9技术构建蛋白磷酸2调节亚基B″家族α亚型(PPP2R3A)基因敲除小鼠,从分子水平及组织水平上研究PPP2R3A缺失对心脏的影响。方法 将Cas9 mRNA和两个靶向PPP2R3A第3外显子翻译起始密码子附近区域的单导向RNA微注射到C57BL/6小鼠受精卵中。小鼠出生后取其基因组DNA进行聚合酶链反应(PCR)和测序以鉴定基因型,鉴定后,基因PPP2R3A缺失型小鼠为KO组,野生型C57BL/6小鼠为WT组(雄性3只,雌性2只)。小鼠心脏组织经甲醛固定并制成切片后分别进行苏木素-伊红(HE)染色和免疫组织化学染色。提取小鼠心脏组织总RNA和蛋白,应用荧光定量PCR和Western印迹验证基因敲除小鼠的有效性和检测互作蛋白表达。结果 获得F1代PPP2R3A杂合小鼠,PCR和测序结果表明突变小鼠的基因型存在113 bp的缺失突变。与WT组相比,KO组心脏组织中PPP2R3A mRNA和蛋白表达量明显下降(均P<0.05),参与心脏发育的G蛋白信号转导调控因子(RGS)19表达量明显升高(P<0.05)。PPP2R3A蛋白表达受损引起了心脏组织病理学变化。结论 PPP2R3A在体内可能通过与RGS19蛋白互作来参与心脏的发育并对心脏功能产生影响。

丁酸盐在炎症性肠病中的免疫调节机制研究进展

炎症性肠病(IBD)是一组与肠道慢性炎症相关的异质性疾病,丁酸盐是肠道微生物群产生的关键代谢产物,能够调节免疫细胞的发育和功能,调节免疫功能并防止过度免疫反应,从而延缓IBD的临床进展。本文就丁酸盐在调节免疫功能方面改善IBD作用机制的研究进展进行综述,旨在为IBD的临床治疗提供新的选择。

植物异三聚体G蛋白研究进展

植物细胞中的异三聚体G蛋白信号转导系统包括异三聚体G蛋白、G蛋白偶联受体、类受体激酶、G蛋白信号调节因子等,这些信号转导组分在感受物理及化学刺激、启动细胞内信号级联反应、调控细胞内代谢和基因表达过程中发挥重要作用.异三聚体G蛋白参与调控植物生长发育(如胚胎形成、营养器官生长、有性生殖等)、植物对生物及非生物胁迫的响应、根瘤形成等过程.因此,异三聚体G蛋白信号系统组分参与调控多种农作物的农艺性状,并最终影响农产品的产量和品质.对植物异三聚体G蛋白的结构、活化机制和生理功能等方面近年来取得的研究进展进行了回顾和总结.

黏附性G蛋白偶联受体F1在胰腺导管腺癌中的表达及其促进癌症进展的机制研究

目的·分析黏附性G蛋白偶联受体F1(adhesion G protein-coupled receptor F1,ADGRF1)在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)发生及发展过程中的表达变化,探究ADGRF1对PDAC细胞增殖的影响以及促进PDAC进展的潜在分子机制。方法·基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库和基因表达综合(Gene Expression Omnibus,GEO)数据库分析ADGRF1在正常胰腺组织及PDAC组织中的mRNA水平表达。利用实时荧光定量PCR(quantitative real-time PCR,qPCR)和蛋白质印迹法(Western blotting)检测ADGRF1在正常胰腺导管上皮细胞hTERT-HPNE及多种PDAC细胞中的表达情况。利用免疫组织化学染色(immunohistochemistry staining,IHC)检测PDAC患者的癌组织及癌旁组织中ADGRF1的表达差异。转染小干扰RNA(small interfering RNA,siRNA)敲低ADGRF1后,通过CCK8和平板克隆形成实验检测PDAC细胞AsPC-1、SW1990增殖能力的变化。构建稳定过表达ADGRF1的Patu8988细胞,通过CCK8实验检测过表达ADGRF1引起的PDAC细胞增殖变化。利用RNA测序(RNA-sequence,RNA-seq)、基因集富集分析(gene set enrichment analysis,GSEA)和免疫浸润分析预测与ADGRF1促进PDAC癌症进展相关的信号通路。结果·TCGA数据库和GEO数据库的分析结果显示ADGRF1 mRNA在PDAC组织中的表达高于正常胰腺组织(均P=0.000)。qPCR和Western blotting结果显示,与hTERT-HPNE细胞相比,多种PDAC细胞中ADGRF1的mRNA和蛋白水平均有所上调(均P<0.05)。IHC结果显示ADGRF1在PDAC患者癌组织中的表达也高于癌旁组织。此外,下调ADGRF1能够抑制PDAC细胞AsPC-1、SW1990的增殖能力;而过表达ADGRF1则促进Patu8988细胞的增殖能力(均P<0.05)。RNAseq、GSEA富集分析和免疫浸润的结果显示,ADGRF1的表达与干扰素α(interferon-α,IFN-α)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和核因子κB(nuclear factorκB,NF-κB)等信号通路有关。结论·ADGRF1在PDAC细胞和组织中高表达,促进PDAC细胞的增殖,其机制可能与多个免疫相关信号通路有关。

肠道菌群介导次级胆汁酸及其受体调节肠黏膜免疫机制的研究进展

胆汁酸是一种胆固醇衍生物,对提高每日膳食中脂肪的消化与吸收率具有显著功效。在肝内,细胞利用胆固醇形成初级胆汁酸,初级胆汁酸在肠道菌群产生的蛋白酶的影响下产生次级胆汁酸,极大地扩大了肠道环境的分子多样性。目前最常见的次级胆汁酸受体为跨膜G蛋白胆汁酸偶联受体-5(GPBAR1,也被称为TGR5)和核受体法尼类X受体(FXR),在调节机体健康中起着多效性作用,特别是可以维持肠道菌群稳态和黏膜免疫系统平衡。本综述讨论了胆汁酸与肠道菌群的关系、次级胆汁酸的代谢以及次级胆汁酸及其受体在肠道免疫系统中的不同作用机制,可为肠道菌群在动物肠道疾病的防治以及相关研究等方面提供理论基础。