Effect of Cigarette Smoke Extract on the Role of Protein Kinase C in the Proliferation of Passively Sensitized Human Airway Smooth Muscle Cells

Cigarette smoke(CS) is ani mportant risk fac-tor involvedin the development and progression ofasthma[1]. Ovalbumin ( Ova) sensitization inducesairway hyperresponsiveness ( AHR) to inhaled CSin guinea pigs[2]. Airway smooth muscle prolifera-tion plays an i mportant role in airway remodelingin asthma . Protein kinase C (PKC) is one of thecrucial kinases in the intracellular signal transduc-tion pathway .CSEcanincrease PKC's activationinhuman bronchial epithelial cells[3].Because airwaysm…     

The Effects of Protein Kinase C （PKC） on the Tension of Normal and Passively Sensitized Human Airway Smooth Muscle and the Activity of Voltage-dependent Delayed Rectifier Potassium Channel （Kv）

The effects of protein kinase C (PKC) on the tension and the activity of volt- age-dependent delayed rectifier potassium channel (Kv) were examined in normal and passively sen- sitized human airway smooth muscle (HASM), by measuring tones and whole-cell patch clamp tech- niques, and the Kv activities and membrane potential (Em) were also detected. The results showed that phorbol 12-myristate 13-acetate (PMA), a PKC activator, caused a concentration-dependent constric- tion in normal HASM rings. The constriction of the passively sensitized muscle in asthma serum group was significantly higher than that of the normal group (P<0.05), and the constrictions of both groups were completely abolished by PKC inhibitor Ro31-8220 and calcium channel inhibitor nifedipine. Kv activities of HASM cells were significantly inhibited by PMA, and the Em became more positive, as compared with the DMSO (a PMA menstruum)-treated group (P<0.01). This effect could be blocked by Ro31-8220 (P<0.01). It was concluded that activation of PKC could increase the tones of HASM, which might be related to the reduced Kv activity. In passively sensitized HASM rings, this effect was more notable.     

Effects of mitochondrial ATP-sensitive K+ channel on protein kinase C pathway and airway smooth muscle cell proliferation in asthma

The effects of ATP-sensitive mitochondrial K + channel(mitoK ATP) on mitochondrial membrane potential(Δψm),cell proliferation and protein kinase C alpha(PKCα) expression in airway smooth muscle cells(ASMCs) were investigated.Thirty-six Sprague-Dawley(SD) rats were immunized with saline(controls) or ovalbumin(OVA) with alum(asthma models).ASMCs were cultured from the lung of control and asthma rats.ASMCs were treated with diazoxide(the potent activator of mitoK ATP) or 5-hydroxydencanote(5-HD,the inhibitor of mitoK ATP).Rhodamine-123(R-123) was used to detect Δψm.The expression of PKCα protein was examined by using Western blotting,while PKCα mRNA expression was detected by using real-time PCR.The proliferation of ASMCs was measured by MTT assay and cell cycle analysis.In diazoxide-treated normal ASMCs,the R-123 fluorescence intensity,protein and mRNA levels of PKCα,MTT A values and percentage of cells in S phase were markedly increased as compared with untreated controls.The ratio of G 0 /G 1 cells was decreased(P<0.05) in diazoxide-treated ASMCs from normal rats.However,there were no significant differences between the ASMCs from healthy rats treated with 5-HD and the normal control group.In untreated and diazoxide-treated ASMCs of asthmatic rats,the R-123 fluorescence intensity,protein and mRNA levels of PKCα,MTT A values and the percentage of cells in S phase were increased in comparison to the normal control group.Furthermore,in comparison to ASMCs from asthmatic rats,these values were considerably increased in asthmatic group treated with diazoxide(P<0.05).After exposure to 5-HD for 24 h,these values were decreased as compared with asthma control group(P<0.05).In ASMCs of asthma,the signal transduction pathway of PKCα may be involved in cell proliferation,which is induced by the opening of mitoK ATP and the depolarization of Δψm.     

Role of protein kinase C in the activation of store-operated Ca2+ entry in airway smooth muscle cells

Store-operated Ca2+ channels (SOCs) are plasma membrane Ca2+ permeable channels activated by depletion of intracellular Ca2+ store. Ca2+ entry through SOCs is known as store-operated Ca2+ entry (SOCE), which plays an important role in the functional regulation of airway smooth muscle cells (ASMCs). Protein kinase C (PKC) has been shown to have an activating or inhibiting effect on SOCE, depending on cell types and PKC isoforms that are involved. In ASMCs, the effect of PKC on SOCE has not been elucidated so far. In this study, the role of PKC in the activation of SOCE in rat ASMCs was examined by using Ca2+ fluorescence imaging technique. The results showed that acute application of PKC activators PMA and PDBu did not affect SOCE induced by the sarcoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor thapsigargin. The non-selective PKC inhibitor chelerythrine significantly inhibited thapsigargin- and bradykinin-induced SOCE. RT-PCR assay identified PKCα, δ and ε isoforms in rat ASMCs. PKCα-selective inhibitor G6976 and PKCε-inhibiting peptide Epsilon-V1-2 had no effect on SOCE; by contrast, PKCδ-selective inhibitor rottlerin attenuated SOCE dramatically, suggesting that PKCδ was the major PKC isoform involved in the activation of SOCE in ASMCs. Moreover, PKC down-regulation by extended exposure to high doses of PMA or PDBu also reduced SOCE, confirming the essential role of PKC in the activation of SOCE in ASMCs. In addition, PKC down-regulation did not influence the expression of stromal interaction molecule 1 (STIM1) and Orai1, two elementary molecules in the regulation and activation of SOCs. These results identified PKCδ as an essential PKC isoform involved in the activation of SOCE, and confirmed that PKC regulates the function of ASMCs in a SOCE-dependent manner.     

紫草素抑制人气道平滑肌细胞的增殖

目的 研究紫草素对体外培养的人气道平滑肌细胞(HASMCs)增殖的影响.方法 组织块贴壁法原代培养传至4～8代的HASMCs,经40、20、10、5、2、1、0.5 ?mol/L及0 ?mol/L(对照组)的紫草素分别作用12、24、48 h后,应用MTS法测定紫草素对HASMCs的细胞增殖的影响;经40、20、10、5 ?mol/L及0 ?mol／L(对照组)的紫草素分别作用24 h后,应用流式细胞术分析紫草素对细胞周期的影响;经20 ?mol/L及0 ?mol/L(对照组)的紫草素分别作用24 h后,应用SP免疫细胞化学法检测紫草素对增殖细胞核抗原(PCNA)表达的影响.结果 (1)与对照组相比,20 ?mol/L和40 ?mol/L的紫草素均可有效抑制细胞增殖(均P<0.05),以48 h最为显著(抑制率分别为30.1％与42.9％),但两者之间无显著性差异(P0.05).(2)20 ?mol/L及40 ?mol/L的紫草素均可显著提高G0/G1期比例(P<0.05),阻滞细胞周期进程,但两者之间无显著性差异(P0.05).(3)20 ?mol/L的紫草素可显著下调PCNA的表达(P<0.01).结论 紫草素对HASMCs具有明确的抗增殖作用.     

PAI-1对气道平滑肌增殖和ERK表达的影响

目的探讨纤溶酶原激活物抑制物-1（PAI-1）对气道平滑肌增殖的调控作用,以及对细胞外调节蛋白激酶（ERK）表达的影响。方法体外培养小鼠气道平滑肌细胞（ASMCs）并分为7 组：空白对照组、PAI-15 μg/L组、PAI-1 10 μg/L组、PAI-1 20 μg/L 组、PAI-1 40 μg/L组、PAI-1 80 μg/L 组、PAI-1 100 μg/L组。放入37℃培养箱分别培养12、24 和48 h,采用CCK-8 检测ASMCs的A 值,计算增殖率。以增殖率最高的实验组的浓度和作用时间作为PAI-1 作用最适浓度和最适作用时间,进一步分6 组：A组（空白对照）;B 组（PAI-1 20 μg/L）;C 组（PAI-1 40 μg/L）;D 组（PAI-1 80 μg/L）;E 组（PAI-1 100 μg/L）;F 组（PAI-1 最适浓度+ERK 通道抑制剂PD98059 10 μmol/L）,用CCK-8 检测ASMCs 的增殖,Western blot检测ERK 蛋白的表达,实时荧光定量聚合酶链反应检测ERK mRNA 的表达。结果5～100 μg/L PAI-1 作用ASMCs 12、24 和48 h后细胞增殖率结果显示,在相同浓度下,不同时间各组比较,差异有统计学意义（P <0.05）,以48 h时ASMCs增殖率最高;在相同时间下,不同浓度各组比较,差异有统计学意义（P <0.05）,80μg/L PAI-1的ASMCs增殖率最高;故选取48 h为最适作用时间,80μg/L为最适浓度进行后续实验。再次分组的实验结果表明,B、C、D、E组的ERK 磷酸化水平和ERK mRNA 的相对表达量与A 组比较,差异有统计学意义P <0.05）,B、C、D、E组增高;B、C、D、E组两两比较结果显示,除B 组与E 组比较,差异无统计学意义（P >0.05）外,其余各组两两 比较,差异有统计学意义（P <0.05）,当PAI-1 浓度波动于20～80 μg/L 时,ERK 磷酸化水平和ERK mRNA相对表达量随浓度升高而增高,>80 μg/L 后则不再增高;加入PD98059 的F 组与D 组比较,差异有统计学意义（P <0.05）,ERK 磷酸化水平和ERK mRNA表达降低。结论外源性PAI-1 可以通过促进ERK 通路的表达,进而促进ASMCs 的增殖。     

Focal adhesion kinase antisense oligodeoxynucleotides inhibit human pulmonary artery smooth muscle cells proliferation and promote human pulmonary artery smooth muscle cells apoptosis

Background Pulmonary artery smooth muscle cell (PASMC) proliferation plays an important role in pulmonary vessel structural remodelling. At present, the mechanisms related to proliferation of PASMCs are not clear. Focal adhesion kinase (FAK) is a widely expressed nonreceptor protein tyrosine kinase. Recent research indicates that FAK is implicated in signalling pathways which regulate cytoskeletal organization, adhesion, migration, survival and proliferation of cells. Furthermore, there are no reports about the role of FAK in human pulmonary artery smooth muscle cells (HPASMCs). We investigated whether FAK takes part in the intracellular signalling pathway involved in HPASMCs proliferation and apoptosis, by using antisense oligodeoxynucleotides (ODNs) to selectively suppress the expression of FAK protein. Methods Cultured HPASMCs stimulated by fibronectin (4μg/ml) were passively transfected with ODNs, sense FAK, mismatch sense and antisense-FAK respectively. Expression of FAK, Jun NH2-temlinal kinase (JNK), cyclin-dependent kinase 2 (CDK 2) and caspase-3 proteins were detected by immunoprecipitation and Western blots. Cell cycle and cell apoptosis were analysed by flow cytometry. In addition, cytoplasmic FAK expression was detected by immunocytochemical staining. Results When compared with mismatch sense group, the protein expressions of FAK, JNK and CDK 2 in HPASMCs decreased in antisense-FAK ODNs group and increased in sense-FAK ODNs group significantly. Caspase-3 expression upregulated in HPASMCs when treated with antisense ODNs and downregulated when treated with sense ODNs. When compared with mismatch sense ODNs group, the proportion of cells at G1 phase decreased significantly in sense ODNs group, while the proportion of cells at S phase increased significantly. In contrast, compared with mismatch sense ODNs group, the proportion of cells at G1 phase was increased significantly in antisense-FAK ODNs group. The level of cell apoptosis in antisense-FAK group was higher than in the mismatch sense group and the latter was higher than sense-FAK group. In addition, the sense-FAK ODNs group was strongly stained by immunocytochemistry, whereas the antisense-FAK ODNs group was weakly stained. Conclusions The results suggest that FAK relates to the proliferation of HPASMCs Antisense-FAK ODNs inhibit HPASMCs proliferation and facilitate their apoptosis. It is possible that FAK via JNK, CDK 2 signalling pathways enhances HPASMCs proliferation and via caspase-3 inhibits HPASMCs apoptosis.     

The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin Ⅱ

Background Human urotensin Ⅱ (UⅡ) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UⅡ is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UⅡ mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UⅡ. Methods In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UⅡ were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UⅡ was measured using Fura-2/AM. Results UⅡ 10-7 mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P&lt;0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P&lt;0.01). It promoted the cytosolic free calcium concentration increase of 18% (P&lt;0.01). CsA 10-6 mol/L and H7 50 μmol/L inhibited UⅡ-stimulated CaN activity by 45% (P&lt;0.01) and 21% (P&lt;0.05), respectively, while PD98059 50 μmol/L had no effect on CaN activity (P&gt;0.05). CsA 10-6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P&lt;0.05), while having no effect on MAPK activity (P&gt;0.05). Conclusions UⅡ increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.     

高迁移率族蛋白B1对人气道平滑肌细胞增殖和迁移及Akt磷酸化的影响

目的:探讨高迁移率族蛋白B1(high morbility group protein box 1,HMGB1)刺激对人气道平滑肌细胞(human airway smooth muscle cells,HASMC)增殖和迁移的影响及其机制?方法:体外培养HASMC,将纯化的第3~8代细胞随机分为对照组?HMGB1组(125?250?500和1 000 ng/mL)?TGF-β阳性对照组(1 ng/mL),CCK-8法测定HASMC增殖能力,Transwell小室观察HMGB1对 HASMC迁移的影响,Western blot检测HASMC的Akt磷酸化?结果:与对照组相比,HMGB1呈浓度依赖性刺激HASMC增殖(P < 0.05);HMGB1(500 ng/mL)刺激HASMC后,细胞迁移能力显著高于对照组(P < 0.01);HMGB1(500 ng/mL)组HASMC的Akt磷酸化水平较对照组显著增高(P < 0.05)?结论:HMGB1促进HASMC增殖和迁移,可能是通过调节PI3K/Akt通路参与气道重塑,为今后治疗哮喘提供了新思路?     

siRNA 沉默凋亡抑制蛋白基因对支气管哮喘小鼠气道平滑肌增殖的影响

目的：探讨 siRN A 沉默凋亡抑制蛋白基因对支气管哮喘小鼠气道平滑肌增殖的影响。方法将20只雌性BALB／c小鼠分为实验组和对照组,实验组构建哮喘模型,取气管和支气管进行细胞培养。对实验组和对照组培养的气道壁平滑肌细胞分别进行分组：磷酸盐缓冲液（PBS）对照组（加入PBS）、错义链对照组（转染错义链）和siRNA转染组（转染siRNA Sur‐vivin）,检测气道壁平滑肌细胞中 Survivin基因、Survivin蛋白和 caspase‐9蛋白表达,检测细胞上清液中 IL‐6和人趋化因子（CCL5）水平。结果 RT‐PCR结果显示,实验组中siRNA转染组小鼠气道壁平滑肌细胞中Survivin RNA 相对表达量均低于PBS对照组和错义链对照组,气道壁平滑肌细胞中 Survivin蛋白表达量均低于PBS对照组和错义链对照组,而caspase‐9蛋白表达量则高于PBS对照组和错义链对照组,差异均有统计学意义（ P＜0．05）;实验组中siRN A转染组气道壁平滑肌细胞合成分泌IL‐6和CCL5水平均低于PBS对照组和错义链对照组;2～4 d细胞增殖量均低于PBS对照组和错义链对照组;气道壁平滑肌细胞G0／G1期比例高于PBS对照组和错义链对照组,而S／G2期比例则低于PBS对照组和错义链对照组,细胞凋亡率则高于 PBS对照组和错义链对照组,差异均有统计学意义（P＜0．05）。结论 siRNA特异性沉默Survivin基因,可加速气道壁平滑肌细胞凋亡,有效抑制细胞异常增殖及分泌功能。     

穹窿主体蛋白对血管平滑肌细胞增殖的影响

目的:探讨穹窿主体蛋白(major vault protein,MVP)对血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响?方法:分离培养野生型小鼠VSMCs,用血小板源性生长因子(PDGF-BB)或15% 胎牛血清(FBS)刺激VSMCs增殖,Western blot检测VSMCs的MVP表达水平,同时检测特异性分化标记物α-SMA和SM22α表达水平?然后用PDGF-BB刺激人主动脉平滑肌细胞(HAoSMCs),检测MVP的表达差异?再分别分离培养野生型小鼠和MVP敲除型小鼠的VSMCs,通过CCK8细胞增殖实验检测两者的增殖能力;同时用siRNA干扰的方法,使HAoSMCs中MVP低表达,检测其增殖能力的变化?结果:用PDGF-BB或15% FBS刺激VSMCs后,MVP表达水平呈浓度和时间依赖性下降,α-SMA和SM22α表达水平也相应降低?MVP缺失或低表达情况下,VSMCs的增殖能力均下降?结论:MVP在VSMCs增殖中起了重要作用?     

Anti-miR-145促进人气道平滑肌细胞增殖及骨桥蛋白合成

目的观察miR-145抑制剂（Anti-miR-145）对人支气管平滑肌细胞（HASMCs）的影响,探讨其在哮喘气道重塑中的作用。
方法分为对照组和实验组,实验组加入不同浓度的Anti-miR-145（10~100 nmol/L）。CCK-8法检测细胞增殖,流式细胞术检测
细胞凋亡,Western blotting 检测骨桥蛋白合成。结果与对照组比较,10 nmol/L和50 nmol/L Anti-miR-145显著促进HASMCs
增殖及骨桥蛋白合成（P<0.05或P<0.01）,50 nmol/L Anti-miR-145 显著抑制HASMCs 凋亡（P<0.01）。结论Anti-miR-145通过
刺激HASMCs增殖和骨桥蛋白合成,抑制其凋亡,可能在哮喘气道重塑中发挥重要作用。
     

粉防已碱抑制气道平滑肌细胞增殖活性的作用

目的 :粉防已碱 (Tet)是中药源的胞膜Ca2 + 通道拮抗剂 ,本研究拟探讨Tet对气道平滑肌细胞 (ASMC)增殖活性的影响及机制 .方法 :采用含胎牛血清的DMEM原代培养BALB/c小鼠ASMC ,3 H TdR掺入法检测不同剂量Tet(1 0和4 0mg·L-1 )对ASMC增殖活性的影响 ,以及台盼蓝染色法检测ASMC活细胞的数量 .激光共聚焦显微镜下观察组胺对ASMC中 [Ca2 + ]i的促升高作用 ,以及Tet对这种促升高作用的干预效应 .结果 :与正常对照组相比 ,Tet明显抑制了ASMC的增殖活性 ,并呈现剂量依赖性 .Tet对组胺激发的[Ca2 + ]i升高表现出明显抑制效应 .结论 :TET能有效抑制培养ASMC的增殖活性 ,这种作用是通过阻断胞膜Ca2 + 通道而降低 [Ca2 + ]i实现的     

缺氧促使鼠气道平滑肌细胞丝裂原活化蛋白酶表达

目的 探讨缺氧情况下鼠气道平滑肌细胞丝裂原活化蛋白激酶（mitogen activated protein kinase,MApK）的变化.方法 雄性Wistar大鼠采用缺氧方法,用随机数字表法随机分为正常对照组、缺氧4周组,每组6只.按实验要求完成缺氧时间,12 h内留取肺叶组织,行免疫组织化学.结果 免疫组织化学染色显示,对照组大鼠肺小动脉内膜有散在免疫阳性染色,低氧组大鼠肺气道内膜则可见明显的免疫阳性染色.经灰度扫描,低氧组大鼠肺气道壁MAPK免疫染色阳性强度较对照组明显增强（P＜0.01）.结论 MAPK在缺氧性肺病引起的气道平滑肌细胞增生中可能起着重要作用.     

当归抑制人肺血管平滑肌细胞黏着斑激酶的表达

目的探讨当归对肺血管平滑肌细胞黏着斑激酶（FAK）的影响。方法实验分成4组。对照组：不加任何干预因素；fibronection（FN）组：（作为刺激剂）40μg／mL；当归组：3mg／mL；联合组：FN40μg／InL＋当归组：3mg／mL。采用免疫印迹方法检测了FAK蛋白质的表达，应用Tunel法检测细胞凋亡的变化。结果FAK（蛋白质在对照组与当归组中无表达，在FN组中，FAK蛋白质呈高表达；FAK蛋白质在混合组（当归＋FN组）中表达降低，与FN组比较差异具有显著性（P〈0．01）；Tunel法检测细胞凋亡表明当归组细胞凋亡明显增加。结论当归通过减少FAK形成抑制肺血管平滑肌细胞增生，促进细胞凋亡，在防治肺血管平滑肌细胞增生方面有着重要的作用。     

姜黄素抑制大鼠气道平滑肌细胞增殖的作用

目的 研究姜黄素对气道平滑肌细胞(airway smooth muscle cells,ASMCs)增殖的作用.方法 体外培养大鼠原代ASMCs.CCK-8法检测血小板源生长因子(platelet-derived growth factor,PDGF)和PDGF加姜黄素处理的ASMCs A150的光密度值,以观察PDGF诱导的增殖和姜黄素的抗增殖作用.Western blotting 检测ERK1/2蛋白的表达水平.结果 与对照组(1.04±0.12)比较,CCK-8法检测给予PDGF 2 d后,10ng/mL PDGF组(1.16±0.14)和50 ng/mL PDGF组(1.30±0.15)的A150的光密度值均显著增加.P＜0.01.给予姜黄素处理12、24和36 h后,与对照组比较,11.25μmol/L组(21.57%、43.55%和65.99%)、16.88μmol/L组(39.64%、57.44%和77.80%)和25.3μmol/L组(44.50%、53.68%和92.68%)的细胞平均抑制率均增加显著,P＜0.05.姜黄素(25μmol/L)加PDGF(25 ng/mL)处理20、40和60 min后ERK1/2蛋白表达水平均显著降低.结论 姜黄素对增殖的ASMCs有抑制作用,可能与抑制了ERK1/2的信号通路活化有关.     

The regulating effects of protein kinase C on the tone of guinea-pig trachea and human lobus bronchi

Summary The regulating effects of protein kinase C (PKC) on the tone of guinea-pig trachea and human lobus bronchi were investigated by measuring the tone of isolated tracheal and bronchial strips. The effects of PKC on the tone of guinea-pig tracheal and human lobus bronchi were observed and compared. The results showed that: (1) PKC activator PMA induced concentration-dependent relaxation in guinea-pig isolated trachea strips. This relaxation was completely ablated by the pretreatment with 5 × 10^t-6mol/L Ro31-8220 which is a PKC-specific inhibitor, but was not affected by the removal of epithelium (EP), or by the pretreatment with propranolol (β-receptor blocker) or atropin (M-receptor blocker); (2) PMA led to concentration-dependent contraction in human lobus bronchi. This contractile response was completely depressed by the pretreatment with 5 × 10^t-6 mol/L Ro31-8220 and was partly inhibited by 1 × 10^t-5 mol/L isoptin (Ca²⁺-antagonist). but was not significantly affected by propranolol or atropin. It is concluded that PKC is involved in the regulation of airway smooth muscle tone. The regulating effects may vary in different animals.     

Effects of pinacidil on proliferation of cultured rabbit airway smooth muscle cells induced by endothelin-1

It has been found that the potassium channel dysfunction of the membrane of airway smooth muscle cells (ASMCs) is closely associated with proliferation of ASMCs. Preliminary research has demonstrated that pinacidil, an ATP sensitive potassium channel (KATP) opener, could play a remarkable role in the prevention and treatment of antigen induced bronchial asthma in guinea pigs.     

Effect of vascular endothelial growth factor and its receptor KDR on human airway smooth muscle cells proliferation

Airway remodeling with inflammatory cell infiltration, epithelial shedding, basement membrane thickening and increased mass of airway smooth muscle (ASM) is an important determinant of bronchial obstruction and hyperresponsiveness in asthma. Increased ASM mass is by far the most important abnormality responsible for excessive airway narrowing and compliance of the airway wallin asthma.