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Airway smooth muscle cells from ovalbumin-sensitized mice show increased proliferative response to TGFß1 due to upregulation of Smad3 and TGFßRII.

Shi, Jianting; Chen, Ming; Ouyang, Lihua; Huang, Linjie; Lin, Xiaoling; Zhang, Wei; Liang, Ruiyun; Lv, Zhiqiang; Liu, Shanying; Jiang, Shanping.
J Asthma; 54(5): 467-475, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27905842

OBJECTIVE:

This study aimed to elucidate the role of Transforming growth factor (TGF)-ß1 signaling in the proliferation of airway smooth muscle cells (ASMCs).

BACKGROUND:

TGF-ß1 is an important cytokine in airway remodeling in asthma. However, results of studies focusing on the effect of TGFß1 on proliferation of ASMCs are controversial.

METHODS:

An allergic model that mimics airway remodeling in chronic asthma was established and primary ASMCs were cultured. Cell proliferation was detected by viable cell counting and Cell Counting Kit (CCK)-8 analysis. Expression and phosphorylation of Smad3, type 1 TGFß receptor (TGFßRI), type 2 TGFß receptor (TGFßRII), extracellular signal-regulated kinase (ERK)-1/2, p38 mitogen-activated protein kinase (MAPK), C-Jun N-terminal kinase (JNK) and AKT were detected by western blot. siRNAs were used to knock down Smad3 and TGFßRII.

RESULTS:

Smad3 and TGFßRII were up-regulated in primary ASMCs isolated from ovalbumin (OVA)-sensitized mice as compared with ASMCs isolated from unsensitized control mice, which persisted for at least four passages. TGFß1 stimulated proliferation of ASMCs isolated from OVA-sensitized mice, which was inhibited by specific siRNA targeting Smad3 or TGFßRII. However ASMCs from control mice showed no proliferative response to TGFß1. TGFß1-induced proliferation of ASMCs from OVA-sensitized mice was markedly attenuated by PD-98059, a specific ERK1/2 inhibitor. TGFß1 induced ERK1/2 phosphorylation within 15 minute, which was partially blocked by specific inhibitor of Smad3 (SIS3).

CONCLUSIONS:

ASMCs isolated from OVA-sensitized mice showed hyper-proliferation upon TGFß1 stimulation. This might have been associated with up-regulated Smad3 and TGFßRII and mediated by ERK1/2 downstream to Smad3.