Differential gene expression analysis in early and late erythroid progenitor cells in β‐thalassaemia

β‐ thalassaemia is a disorder of globin gene synthesis resulting in reduced or absent production of the β‐globin chain in red blood cells. In this study, haematopoietic stem cells were isolated from the peripheral blood of six transfusion dependent β‐thalassaemia patients and six healthy controls. Following 7 and 14 d in culture, early‐ and late‐ erythroblasts were isolated and purified. No morphological difference in maturation was observed following 7 d in culture, while a delayed maturation was observed in the patient group after 14 d. Following RNA isolation and linear amplification, gene expression analyses were performed using microarray technology. The generated data were analysed by two methods: the BRB‐ArrayTools platform and the Bioconductor platform using bead level data. Following 7 d culture, there was no difference in gene expression between the control and patient groups. Following 14 d culture, 384 differentially expressed genes were identified by either analysis. A subset of 90 genes was selected and the results were confirmed by Quantitative‐Real‐Time‐polymerase chain reaction. Pathways shown to be significantly altered in the patient group include apoptosis, MAPKinase and the nuclear factor‐κB pathway.     

Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers

Inositol polyphosphate 4-phosphatase-II (INPP4B) is a regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway and is implicated as a tumor suppressor in epithelial carcinomas. INPP4B loss of heterozygosity (LOH) is detected in some human breast cancers; however, the expression of INPP4B protein in breast cancer subtypes and the normal breast is unknown. We report here that INPP4B is expressed in nonproliferative estrogen receptor (ER)-positive cells in the normal breast, and in ER-positive, but not negative, breast cancer cell lines. INPP4B knockdown in ER-positive breast cancer cells increased Akt activation, cell proliferation, and xenograft tumor growth. Conversely, reconstitution of INPP4B expression in ER-negative, INPP4B-null human breast cancer cells reduced Akt activation and anchorage-independent growth. INPP4B protein expression was frequently lost in primary human breast carcinomas, associated with high clinical grade and tumor size and loss of hormone receptors and was lost most commonly in aggressive basal-like breast carcinomas. INPP4B protein loss was also frequently observed in phosphatase and tensin homolog (PTEN)-null tumors. These studies provide evidence that INPP4B functions as a tumor suppressor by negatively regulating normal and malignant mammary epithelial cell proliferation through regulation of the PI3K/Akt signaling pathway, and that loss of INPP4B protein is a marker of aggressive basal-like breast carcinomas.     

紫草素对HepG2细胞增殖、凋亡和PI3K/Akt/NF-κB信号通路蛋白表达的影响*

目的 研究紫草素对肝癌HepG2细胞增殖、凋亡和磷脂酰肌醇3-激酶(PI3K)/蛋白激酶(Akt)/核转录因子-κB(NF-κB)信号通路的影响。方法 以0(对照)、1、2.5和5 μmol/L紫草素分别处理对数生长期的HepG2细胞48 h,分别采用MTT法检测细胞增殖,使用流式细胞仪检测细胞凋亡,采用Western blot法检测凋亡相关蛋白(Bax、Bcl-2、Caspase-3)、细胞自噬相关蛋白(LC3-I、LC3-II、p62)和PI3K/Akt/NF-κB通路蛋白表达情况。结果 自小剂量、中剂量到大剂量,紫草素处理HepG2细胞增殖抑制率分别为(23.7±3.5)%、(36.2±6.1)%和(56.9±8.3)%,均显著高于对照组[(0.0±0.0)%,P<0.05],细胞凋亡率分别为(19.2±5.3)%、(37.4±7.6)%和(58.6±8.8)%,均显著高于对照组[(2.5±1.2)%,P<0.05];细胞凋亡相关蛋白表达Bax/Bcl-2比值和Caspase-3相对表达量分别为(1.3±0.2)和(2.7±0.3)、(8.2±0.6)和(0.45±0.10)和(0.78±0.16)和(0.95±0.21),显著高于对照组[分别为(0.6±0.1)和(0.18±0.06),P<0.05];细胞自噬相关蛋白表达LC3-II/LC3-I比值为(1.25±0.08)、(1.43±0.10)和(1.76±0.22),显著高于对照组[(0.96±0.08),P<0.05],p62相对表达水平分别为(0.81±0.09)、(0.62±0.15)和(0.43±0.08),显著低于对照组[(1.06±0.05),P<0.05]; PI3K、Akt和p65蛋白表达水平分别为【(0.64±0.16)、(0.51±0.12)和(0.32±0.06)】、(【0.54±0.17)、(0.37±0.05)和(0.05±0.01)】和【(0.63±0.15)、(0.52±0.10)和(0.36±0.09)],均显著低于对照组[分别为(0.84±0.13)、(0.76±0.15)和(0.89±0.11),P<0.05]。结论 紫草素可能通过抑制PI3K/Akt/NF-κB信号通路关键蛋白表达促进HepG2细胞凋亡和自噬,从而具有抑瘤作用。     

PI3K/Akt信号转导通路与脑缺血后细胞凋亡

细胞凋亡为脑缺血时细胞死亡的重要形式之一.磷脂酰肌醇-3激酶(phosphoinositide-3 kinase,PI3K)/丝氨酸-苏氨酸蛋白激酶(serine/threonine kinase,Akt)为重要的细胞存活信号通路,c-Jun氨基端激酶(c-jun N-terminal kinase,JNK)为重要的促进细胞凋亡信号通路.这两大通路转导信号的动态平衡维持着生理状态下的细胞生存与凋亡.脑缺血刺激打破了这一生理平衡,导致大量神经细胞凋亡.多种确切的神经保护因素都与增强细胞存活信号的放大或抑制凋亡信号的放大有关,从而维持这2个通路信号的平衡.     

磷脂酰肌醇3-激酶/蛋白激酶B信号通路对CD40介导胃癌细胞侵袭与转移的研究

目的 探讨可溶性CD40配体(sCD40L)联合磷脂酰肌醇3-激酶/蛋白激酶B(P13K/Akt)信号通路特异性阻断剂LY294002对胃癌AGS细胞体外增殖及侵袭、转移的影响;初步探讨其可能的作用机制.方法 将细胞分成对照组(仅加入含10%胎牛血清的RPMI 1640培养液)、LY294002组(20μmol/L)、sCD40L组(2μg/ml)和LY294002+sCD40L组.四甲基偶氮唑盐法检测不同浓度sCD401,及联合LY294002对细胞增殖的影响;Transwell实验和划痕实验分析细胞侵袭、转移能力的改变;Western印迹检测细胞P13K、p-Akt、血管内皮生长因子(VEGF)蛋白表达的变化.结果 LY294002作用后细胞生存率为65.7%,sCD40L作用后为70.1%,LY294002+sCD40L组生存率为41.3 0A,差异有统计学意义(P<0.05).LY294002+sCD40L组细胞的划痕愈合速度较sCD40L和LY294002组明显减慢.LY294002+sCD40L组平均每个视野的细胞数较sCD40L和LY294002组明显减少.与对照组相比,sCD40L使P13K、p-Akt、VEGF蛋白表达升高,与LY294002联合作用后,P13K,p-Akt、VEGF蛋白表达明显降低.结论 阻断P13K/Akt信号途径可显著增强sCD40L对人胃癌AGS细胞增殖及侵袭、转移的抑制作用,为胃癌的生物治疗提供一种新的方法.     

肝癌细胞中PI3K信号通路对骨桥蛋白表达的影响

目的研究磷脂酰肌醇3-激酶（P13K）信号通路在肝癌细胞骨桥蛋白（OPN）表达调控中的作用。方法体外培养高转移性人肝癌细胞株HCCLM3,分为对照组、P13K特异性抑制剂LY294002浓度5、10、20μmol／L组,处理6h后,采用逆转录聚合酶链反应（RT—PCR）技术检测OPNmRNA表达的变化。结果LY294002可使肝癌细胞HCCLM3的OPNmRNA的表达下降,且这种抑制作用随着LY294002浓度增大而增大（P〈0．01）,呈现剂量依赖性关系。结论LY294002可以抑制肝癌细胞株HCCLM3中OPN的表达,肝癌细胞OPN的表达调控受P13K信号通路调控。     

Proliferation of cardiomyocytes derived from human embryonic stem cells is mediated via the IGF/PI 3-kinase/Akt signaling pathway

Cardiomyocytes from common experimental animals rapidly exit the cell cycle upon isolation, impeding studies of basic cell biology and applications such as myocardial repair. Here we examined proliferation of cardiomyocytes derived from human and mouse embryonic stem (ES) cells. While mouse ES cell-derived cardiomyocytes showed little proliferation, human cardiomyocytes were highly proliferative under serum-free conditions (15-25% BrdU+/sarcomeric actin+). The cells exhibited only a small serum dose-response, and proliferation gradually slowed with increasing differentiation of the cells. Neither cell density nor different matrix attachment factors affected cardiomyocyte proliferation. Blockade of phosphatidylinositol 3-kinase (PI 3-kinase) and Akt significantly reduced cardiomyocyte proliferation, whereas MEK inhibition had no effect. Antibody blocking of the insulin-like growth factor-1 (IGF-1) receptor significantly inhibited cardiomyocyte proliferation, while addition of IGF-1 or IGF-2 stimulated cardiomyocyte proliferation in a dose-dependent manner. Thus, cardiomyocytes derived from human ES cells proliferate extensively in vitro, and their proliferation appears to be mediated primarily via the PI 3-kinase/Akt signaling pathway, using the IGF-1 receptor as one upstream activator. This system should permit identification of regulatory pathways for human cardiomyocyte proliferation and may facilitate expansion of cardiomyocytes from human ES cells for therapeutic purposes.     

Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells

The prevalence of diabetes has exponentially increased in recent decades due to environmental factors such as nocturnal lifestyle and aging, both of which influence the amount of melatonin produced in the pineal gland. The present study investigated the effect of melatonin on signaling pathways of glucose transport in C2C12 mouse skeletal muscle cells. Intriguingly, treatment of C2C12 cells with melatonin (1 nm) stimulated glucose uptake twofold increase. Melatonin-stimulated glucose transport was inhibited with co-treatment with the melatonin receptor antagonist luzindole. Furthermore, treatment of stably over-expressed melatonin receptor type 2B containing C2C12 myotubes with melatonin amplified glucose transport c. 13-fold. Melatonin also increased the phosphorylation level of insulin receptor substrate-1 (IRS-1) and the activity of phosphoinositide 3-kinase (PI-3-kinase). However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK), another important glucose transport stimulatory mediator via an insulin-independent pathway, was not influenced by melatonin treatment. Activity of p38 mitogen-activated protein kinase (MAPK), a downstream mediator of AMPK, was also not changed by melatonin. In addition, melatonin increased the expression level of forkhead box A2, which was recently discovered to regulate fatty acid oxidation and to be inhibited by insulin. In summary, melatonin stimulates glucose transport to skeletal muscle cells via IRS-1/PI-3-kinase pathway, which implies, at the molecular level, its role in glucose homeostasis and possibly in diabetes. Additionally, exposure to light at night and aging, both of which lower endogenous melatonin levels may contribute to the incidence and/or development of diabetes.     

Combined targeting of MEK/MAPK and PI3K/Akt signalling in multiple myeloma

So-called RAS-dependent pathways, such as those signalling via mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3K)/Akt, are implicated in proliferation and survival of multiple myeloma (MM) cells. However, the effects of their combined blockade and its potential therapeutic utility for the treatment of RAS-mutated MM have not systematically been analysed. Here, we tested the functional consequences of single versus combined inhibition of the MEK/MAPK and PI3K/Akt pathways in a large series of primary MM samples (n = 55) and MM cell lines (n = 11). Additionally, the anti-myeloma activity of different treatments was analysed with respect to the RAS mutation status. PI3K/Akt blockade was generally more pro-apoptotic than blockade of MEK/MAPK both in cell lines and in primary MM samples. Simultaneous blockade of both pathways led to significantly enhanced anti-myeloma activity in 75% of primary MM samples, whereas the remainder was largely resistant. Resistance to combination blockade was exclusively observed in RAS wildtype cases, whereas sensitivity was noted in RAS wildtype and in RAS mutated MM. These results suggest that oncogenic RAS is a predictor of sensitivity to combination treatment with PI3K/Akt and MEK/MAPK inhibitors and that such an approach might therefore be beneficial for this genetically well-defined subgroup of MM patients.     

肺癌中PI3K／AKT信号通路对Skp2调控机制的研究

目的探讨肺癌中磷脂酰肌醇-3-激酶（P13K）／AKT信号通路对S期激酶相关蛋白2（Skp2）的调控机制。方法体外培养4种类型肺癌细胞系H460、LK2、H446和A549,经LY294002处理细胞24h后实时RT—PCR法检测Skp2基因表达变化;Westernblot检测E2F1蛋白表达变化。结果实时RT—PCR显示LY294002作用后4种肺肿瘤细胞系中skp2基因表达均下降;Westernblot结果表明在小细胞肺癌、肺鳞癌、大细胞肺癌中E2F1蛋白表达降低,肺腺癌中E2F1蛋白未表达。结论肺癌中P13K／AKT通路可在转录水平调节Skp2表达,在小细胞肺癌、肺鳞癌、大细胞肺癌中此种调节可能通过转录因子E2F1发挥作用,而肺腺癌中E2F1不参与此种调节。     

Impaired PI3K/Akt signal pathway and hepatocellular injury in high-fat fed rats

AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.     

Involvement of PI3K and ERK1/2 pathways in hepatocyte growth factor-induced cholangiocarcinoma cell invasion

AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility were investigated in two human CCA cell lines,HuCCA-1 and KKU-M213,using Transwell in vitro assay.Levels of proteins of interest and their phosphorylated forms were determined by Western blotting.Localization of E-cadherin was analyzed by immunofluorescence staining and visualized under confocal m...     

Leptin stimulates alpha1(I) collagen expression in human hepatic stellate cells via the phosphatidylinositol 3-kinase/Akt signalling pathway.

BACKGROUND/AIMS: Leptin has been recognized as a profibrogenic hormone in the liver and is involved in collagen type I formation by activated hepatic stellate cells (HSCs) in response to fibrogenic substances, but the molecular signal mechanisms by which leptin promotes liver fibrogenesis through upregulation of collagen type I expression is not clear. We investigated whether leptin-induced collagen type I is mediated by the Janus kinase-phosphatidylinositol 3-kinase-Akt (JAKs-PI3K-Akt) pathway in a human HSC cell line, LX-2. METHODS: LX-2 cells were treated with or without various inhibitors in the presence of leptin. RESULTS: Leptin increased alpha1(I) collagen mRNA and protein. JAK1, PI3K and Akt were activated after leptin stimulation. AG490, a JAK inhibitor, blocked JAK1 phosphorylation accompanied by inhibition of PI3K and Akt activation as well as alpha1(I) collagen mRNA expression, indicating a JAK1-dependent mechanism. Wortmannin, a PI3K inhibitor, prevented PI3K and Akt activation and resulted in suppression of alpha1(I) collagen mRNA expression, suggesting a PI3K-mediated process. These changes were reproduced by overexpression of the dominant-negative p85alpha mutant. A443654.3, an Akt inhibitor, opposed Akt activation, leading to downregulation of alpha1(I) collagen mRNA. Overexpression of the dominant-negative Akt mutant led to similar alterations. CONCLUSION: Leptin has a direct action on liver fibrogenesis by stimulating alpha1(I) collagen production in activated HSC. The process appears to be mediated by the PI3K/Akt pathway through activated JAK1.     

胰岛素对人肝细胞L02水通道蛋白9表达的影响及其调控通路

目的 探讨胰岛素对人肝细胞株L02细胞膜上水通道蛋白9(AQP9)表达的调控及其调控通路. 方法 体外培养正常人肝细胞L02,分别给予磷脂酰肌醇3激酶(PI3K)抑制剂LY294002、丝/苏氨酸激酶(AKT)抑制剂A-4-43654,丝裂酶原激活蛋白激酶(MAPK)抑制剂SB2030580及不同浓度胰岛素干预,逆转录-聚合酶链反应及Western blot检测肝细胞AQP9的mRNA和蛋白质表达.组间数据比较采用单因素方差分析.结果 从胰岛素100 nmol/L开始,AQP9的mRNA和蛋白质表达降低(分别为0.55±0.08和0.59±0.08),胰岛素浓度为500 nmol/L时降低最明显(分别为0.39±0.05和0.40±0.06),与对照组相比,差异有统计学意义(P值均<0.05).从胰岛素作用后3 h开始,AQP9转录逐渐降低,12 h时抑制作用明显,AQP9的InRNA和蛋白质相对表达量分别为0.53±0.08和0.54±0.08(P值均<0.05).PI3K抑制剂LY294002及AKT抑制剂A-443654能有效阻断胰岛素对AQP9表达的影响;而MAPK抑制剂SB2030580则对胰岛素刺激AQP9表达无明显作用. 结论 人正常肝细胞膜上AQP9的表达受胰岛素调控,且与PI3K-AKT通道相关.     

黄连温胆汤调控PI3K/Akt/mTOR信号通路干预ApoE-/-小鼠动脉粥样硬化的作用机制

目的观察黄连温胆汤对载脂蛋白E(ApoE)^-/-小鼠动脉粥样硬化的干预效应,从磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物西罗莫司靶蛋白(mTOR)信号通路探讨其机制。方法采用高脂饲料饲养ApoE^-/-小鼠4周构建动脉粥样硬化模型。采用全自动生化分析仪检测小鼠血脂水平;采用苏木精-伊红(HE)染色、油红O染色、Masson染色观察主动脉斑块情况;采用免疫组化法检测小鼠主动脉根部PI3K、Akt、mTOR蛋白表达水平。结果与模型组比较,黄连温胆汤高剂量组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)均降低(P<0.05)。HE染色显示:模型组主动脉根部斑块明显,呈易损斑块特征,各给药组斑块有不同程度减轻;油红O和Masson染色显示:与模型组比较,雷帕霉素组、黄连温胆汤高剂量组主动脉根部斑块面积减小,胶原纤维含量升高(P<0.05),易损斑块趋于稳定。蛋白免疫组化结果显示:黄连温胆汤中剂量组、黄连温胆汤高剂量组小鼠主动脉PI3K、Akt、mTOR蛋白表达水平降低(P<0.05)。结论黄连温胆汤具有降脂和抗动脉粥样硬化的作用,其机制可能与抑制PI3K/Akt/mTOR信号通路,诱导巨噬细胞自噬有关。     

Stem cell factor and erythropoietin inhibit apoptosis of human erythroid progenitor cells through different signalling pathways

Erythropoietin (EPO) and stem cell factor (SCF) are two important factors in human erythropoiesis. We have recently demonstrated that SCF and EPO synergistically activate mitogen-activated protein (MAP) kinase, thereby promoting growth of human erythroid colony-forming cells (ECFCs). In the present study, we have examined the intracellular mechanisms by which SCF and EPO maintain survival of these cells. In the absence of SCF and EPO, human ECFCs underwent rapid apoptosis. The process was significantly inhibited by addition of a single factor and was totally prevented in the presence of both factors. Treatment of ECFCs with wortmannin, a specific inhibitor of phosphoinositide 3-kinase (PI3K), inhibited the antiapoptotic effect of SCF but had no effect on that of EPO, indicating that SCF but not EPO inhibits apoptosis through the PI3K pathway. In contrast, treatment of ECFCs with PD98059, a specific inhibitor of MAP kinase/ERK kinase (MEK), inhibited cell growth but had no effect on the antiapoptotic activity of either SCF or EPO, suggesting that SCF and EPO prevent apoptosis of human ECFCs independent of the extracellular signal-regulated kinase (ERK) pathway. Interestingly, both EPO and SCF induced activation of PI3K. However, through PI3K, SCF caused activation of protein kinase B (PKB), an anti-apoptosis signal, whereas EPO led to activation of ERKs. Furthermore, the SCF- and EPO-maintained expression of antiapoptotic protein Bcl-XL was correlated with the activation of ERKs and was inhibited by PD98059, suggesting that Bcl-XL may not have a major role in preventing apoptosis of human ECFCs. Phosphorylated BAD was not affected by SCF, EPO or wortmannin. Taken together with our previous results, the present study indicates that SCF and EPO support survival and growth of human ECFCs through different signalling pathways and that they transduce distinctly different signals through activation of PI3K.     

牛磺酸通过激活PI3K/Akt信号通路抑制高糖诱导的内皮细胞凋亡

目的 探讨牛磺酸对高糖诱导的内皮细胞凋亡的影响及其信号途径.方法 取健康产妇分娩后12h内的脐带分离人脐静脉内皮细胞(HUVEC),进行细胞培养并分为5组:正常葡萄糖组(5 mmol/LD-葡萄糖,NG组);高糖组(30 mmol/LD-葡萄糖,HG组);NG+TAU组(5mmol/LD-葡萄糖+5 mmol/L牛磺酸);HG+TAU组(30 mmol/L D-葡萄糖+5 mmol/L牛磺酸);HG+TAU+Wo组(30 mmol/LD-葡萄糖+5 mmol/L牛磺酸+50 nmol/L wortmannin).干预48 h后应用流式细胞术检测细胞凋亡情况,Western印迹检测磷酸化蛋白激酶B(p-Akt)蛋白的表达水平,2,7-二氯二氢荧光素二乙酯(H2DCF-DA)探针技术及荧光倒置显微镜检测活性氧簇的相对含量.结果 与NG组相比,HG组细胞的凋亡率显著增加(P＜0.05).与HG组相比,HG+TAU组的凋亡率下降(P＜0.05).与HG+TAU组相比,HG+TAU+Wo组的凋亡率较高(P＜0.05).与NG组相比,HG组磷酸化-Akt蛋白表达下降(P＜0.05).与HG组比较,HG+TAU组磷酸化-Akt蛋白表达增加(P＜0.05).与HG+TAU组相比,HG+TAU+Wo组磷酸化-Akt蛋白表达下降(P＜0.05).牛磺酸可降低高糖诱导的活性氧簇生成(P＜0.05),这一作用亦可被wortmannine所阻断(P＜0.05).结论 牛磺酸通过PI3K/Akt信号途径调节细胞内活性氧簇生成,进而在高糖环境下发挥其抗凋亡作用.     

磷脂酰肌醇3激酶信号转导途径及在支气管哮喘中的作用

磷脂酰肌醇3激酶（PI3K）信号转导通路是参与支气管哮喘（哮喘）发病机制的一条重要受体信号转导途径。在哮喘患者体内,通过这一途径影响气道平滑肌的增殖并对T细胞受体和协同刺激因子受体CD28介导的T细胞的分化、生存、活化和细胞因子的产生起了关键性的作用。这一机制的研究旨在阐明PI3K信号转导通路在哮喘气道重构中的作用,以及相应的拮抗剂的研究,为哮喘的治疗提供了新方向。