Expression Of PI3K In Airway Smooth Muscle Cell Of Asthmatic Rat

AIMAsthma, a chronic disease characterized by airway hyperactivity, inflammation, and remodeling. Recently, we have found irreversible or partly irreversible airway obstruction and persistent airway hyperactivity in asthma are caused by airway remodeling, which due predominantly to airway smooth muscle hyperplasia. Diverse stimuli, which include growth factors, plasma- or inflammatory cell-derived mediators, contractile agonists, cytokines, and extracellar matrix protein, induce ASM proliferation. Mitogens act via receptor tyrosine kinase, G protein-coupled receptors, or cytokine receptors, to activate p21ras and stimulate two parallel signaling pathways in ASM cells, namely, the extracellular signal-regulated kinase (ERK) or the phosphatidylinositol 3 kinase (PI3K) pathways. In recent years, we have found PI3K pathways also played an important role in proliferation of ASM besides ERK.PI3K is a key regulator of a variety of cellular functions from cytoskeletal organization, vesicular trafficking, and cell proliferation to apoptosis.PI3K phosphorylates membrane phosphoinositides on the D3 hydroxyl of the inositol ring to form phosphoinositides 3-phosphate, phosphoinositides 3,4-diphosphate, and phosphoinositides 3,4,5-triphosphate. These D3 phosphoinositides function as second messengers and active downstream effectormolecules, such as 70-kDa ribosomal S6 kinase(p70S6K) or members of the Rho family to regulate cell cycle protein expression and thus modulate cell cycle traversal in ASM cells.In view of the important role of PI3K playing in proliferation of ASM, we hope to invest whether PI3K/Akt signal transduction pathway plays some role in airway remodeling of asthma or not. Thus, our study now is to explore the expression of PI3K in ASMC of asthmatic rat ,and then make a cursory judgement on the role of PI3K signal transduction pathway which would play in the airway remodeling of asthma.METHODS16 Wistar rats were divided into two groups, asthma and normal control at random. After establishment of asthmatic model, flowcytometry, immunofluorescence and western blot were applied to detect the growth fraction of ASMC and the expression of PI3K in cultured ASMC from each rat.RESULTSIt was revealed from flowcytometry that the ratio of S + G2/M to total number of cells in asthma group [ (27.90±3.44) % ] was higher than that in the normal control group [ (13±1.56) %, P<0.05]. The expression of PI3K was observed in both asthma and normal control group. However, it was much higher in asthma group than that in normal control group. There is a positive correlation between the expression of PI3K and the growth fraction in ASMC.CONCLUSIONThe increased expression of PI3K might play an important role in regulating the proliferation of ASMC in asthma...