TGF-beta1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases.
TGF-beta1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases.
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DOI：
10.1186/1465-9921-7-2
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发表时间：
2006-01-03
影响因子：
5.8
通讯作者：
Khalil, N
中科院分区：
文献类型：
--
作者：
Chen, G;Khalil, N
哮喘气道重塑是结缔组织蛋白表达增加、气道平滑肌细胞（ASMC）增生和肥大的结果。TGF-β1可增加ASMC的增殖。有丝分裂原活化蛋白激酶（MAPKs）、p38、ERK和JNK的激活对与细胞增殖相关的信号转导至关重要。在本研究中，我们确定了磷酸化的MAPKs在TGF-β1诱导的ASMC增殖中的作用。用TGF-β1处理融合型和生长阻滞型牛ASMCs。用[3H]-胸腺嘧啶掺入法和细胞计数法测定细胞增殖。Western分析磷酸化p38、ERK1/2和JNK的表达。TGF-β1以浓度依赖的方式增加ASMCs [3H]-胸苷结合和细胞数量。TGF-β1也能增强血清诱导的ASMC增殖。虽然TGF-β1培养的ASMCs磷酸化的p38、ERK1/2和JNK显著增加，但TGF-β1培养后，每种MAPK的最大磷酸化发生时间各不相同。TGF-β1诱导的DNA合成分别被p38和MAP激酶（MEK）的选择性抑制剂SB 203580和PD 98059抑制。抗EGF、FGF-2、igf - 1和PDGF的抗体不抑制TGF-β1诱导的DNA合成。我们的数据表明，ASMCs在TGF-β1的作用下增殖，TGF-β1是由p38和ERK1/2磷酸化介导的。这些发现提示，在哮喘患者气道中表达的TGF-β1可能通过促进ASMC增殖而参与气道不可逆重塑。
Airway remodeling in asthma is the result of increased expression of connective tissue proteins, airway smooth muscle cell (ASMC) hyperplasia and hypertrophy. TGF-β1 has been found to increase ASMC proliferation. The activation of mitogen-activated protein kinases (MAPKs), p38, ERK, and JNK, is critical to the signal transduction associated with cell proliferation. In the present study, we determined the role of phosphorylated MAPKs in TGF-β1 induced ASMC proliferation. Confluent and growth-arrested bovine ASMCs were treated with TGF-β1. Proliferation was measured by [3H]-thymidine incorporation and cell counting. Expressions of phosphorylated p38, ERK1/2, and JNK were determined by Western analysis. In a concentration-dependent manner, TGF-β1 increased [3H]-thymidine incorporation and cell number of ASMCs. TGF-β1 also enhanced serum-induced ASMC proliferation. Although ASMCs cultured with TGF-β1 had a significant increase in phosphorylated p38, ERK1/2, and JNK, the maximal phosphorylation of each MAPK had a varied onset after incubation with TGF-β1. TGF-β1 induced DNA synthesis was inhibited by SB 203580 or PD 98059, selective inhibitors of p38 and MAP kinase kinase (MEK), respectively. Antibodies against EGF, FGF-2, IGF-I, and PDGF did not inhibit the TGF-β1 induced DNA synthesis. Our data indicate that ASMCs proliferate in response to TGF-β1, which is mediated by phosphorylation of p38 and ERK1/2. These findings suggest that TGF-β1 which is expressed in airways of asthmatics may contribute to irreversible airway remodeling by enhancing ASMC proliferation.
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DOI：
10.1152/ajplung.2001.280.5.l999
发表时间：
2001-05-01
影响因子：
4.9
作者：
Coutts, A;Chen, G;Khalil, N
通讯作者：
Khalil, N
DOI：
10.1165/ajrcmb.21.1.3542
发表时间：
1999-07-01
影响因子：
6.4
作者：
Lew, DB;Dempsey, BK;Malik, KU
通讯作者：
Malik, KU
影响因子：
64.5
作者：
BATTEGAY, EJ;RAINES, EW;ROSS, R
通讯作者：
ROSS, R
影响因子：
2.3
作者：
Chen, G;Khalil, N
通讯作者：
Khalil, N
DOI：
10.1152/ajplung.2000.278.3.l545
发表时间：
2000-03-01
影响因子：
4.9
作者：
Cohen, P;Rajah, R;Herrick, DJ
通讯作者：
Herrick, DJ