TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000221930
  • Gene Name:TGFB1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:SB216763
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:chronic obstructive pulmonary disease
  • Tissue:tissues

Other information

  • Title:Glycogen synthase kinase-3 (GSK-3) regulates TGF-β?-induced differentiation of pulmonary fibroblasts
  • Journal:British Journal of Pharmacology
  • Published:2013
  • PubMed ID:23297769
  • Abstract:Background:Chronic lung diseases such as asthma, COPD and pulmonary fibrosis are characterized by abnormal extracellular matrix (ECM) turnover. TGF-β is a key mediator stimulating ECM production by recruiting and activating lung fibroblasts and initiating their differentiation process into more active myofibroblasts. Glycogen synthase kinase-3 (GSK-3) regulates various intracellular signalling pathways; its role in TGF-β?-induced myofibroblast differentiation is currently largely unknown. Purpose:To determine the contribution of GSK-3 signalling in TGF-β?-induced myofibroblast differentiation. Experimental approach:We used MRC5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD. Protein and mRNA expression were determined by immunoblotting and RT-PCR analysis respectively. Results:Stimulation of MRC5 and primary human lung fibroblasts with TGF-β? resulted in time- and dose-dependent increases of α-sm-actin and fibronectin expression, indicative of myofibroblast differentiation. Pharmacological inhibition of GSK-3 by SB216763 dose-dependently attenuated TGF-β?-induced expression of these myofibroblasts markers. Moreover, silencing of GSK-3 by siRNA or pharmacological inhibition by CT/CHIR99021 fully inhibited the TGF-β?-induced expression of α-sm-actin and fibronectin. The effect of GSK-3 inhibition on α-sm-actin expression was similar in fibroblasts from individuals with and without COPD. Neither smad, NF-κB nor ERK1/2 were involved in the inhibitory actions of GSK-3 inhibition by SB126763 on myofibroblast differentiation. Rather, SB216763 increased the phosphorylation of CREB, which in its phosphorylated form acts as a functional antagonist of TGF-β/smad signalling. Conclusion and implication:We demonstrate that GSK-3 signalling regulates TGF-β?-induced myofibroblast differentiation by regulating CREB phosphorylation. GSK-3 may constitute a useful target for treatment of chronic lung diseases.
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