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DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways

  • Authors:
    • Chun-Lian Liang
    • Xiu-Li Li
    • Xiao-Juan Quan
    • Lin Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Geriatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
    Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 183
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    Published online on: March 10, 2023
       https://doi.org/10.3892/etm.2023.11882
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Abstract

Idiopathic pulmonary fibrosis (IPF) is a heterogeneous lung disease associated with high mortality. Disabled‑2 (DAB2), an adapter protein, regulates cell‑fibrinogen adhesion and fibrinogen uptake. DAB2 is differentially expressed in mouse fibrotic lungs induced by bleomycin according to a genome microarray analysis based on Gene Expression Omnibus database. However, the role of DAB2 in IPF has not been revealed. A bleomycin‑induced mouse model of pulmonary fibrosis was constructed in the present study. It found that the expression of DAB2 was upregulated in bleomycin‑induced fibrotic lung tissue with collagen fiber deposition and pulmonary interstitium thickening. Colocalization of DAB2 with α‑smooth muscle actin (SMA) was observed in lung tissue sections. In vitro, human lung fibroblast MRC‑5 cells were treated with TGF‑β1 and the expression of DAB2 was increased. Knockdown of DAB2 suppressed cell proliferation and the expression of α‑SMA, collagen I, collagen IV and fibronectin in TGF‑β1‑treated MRC‑5 cells. The phosphorylation levels of PI3K and AKT were suppressed in DAB2‑knockdown cells. IGF‑1/IGF‑1R has been reported to promote pulmonary fibrosis and activate the PI3K/Akt signaling. In the present study, the activation of IGF‑1/IGF‑1R signaling pathways in bleomycin‑induced fibrotic lung tissues were positively associated with DAB2 expression. The phosphorylation level of IGF‑1R was increased in MRC‑5 cells with TGF‑β1 treatment, and DAB2 expression was decreased by silencing of IGF‑1R. This suggested that DAB2 might be a downstream target of the IGF‑1R pathway and thus induced PI3K/AKT signaling activation and fibrogenesis. The current study demonstrated the importance of DAB2 in pulmonary fibrosis and suggested the potential of IGF‑1R/DAB2/PI3K in the pathogenesis of IPF.
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Copy and paste a formatted citation
Spandidos Publications style
Liang C, Li X, Quan X and Zhang L: DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways. Exp Ther Med 25: 183, 2023.
APA
Liang, C., Li, X., Quan, X., & Zhang, L. (2023). DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways. Experimental and Therapeutic Medicine, 25, 183. https://doi.org/10.3892/etm.2023.11882
MLA
Liang, C., Li, X., Quan, X., Zhang, L."DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways". Experimental and Therapeutic Medicine 25.4 (2023): 183.
Chicago
Liang, C., Li, X., Quan, X., Zhang, L."DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways". Experimental and Therapeutic Medicine 25, no. 4 (2023): 183. https://doi.org/10.3892/etm.2023.11882
Copy and paste a formatted citation
x
Spandidos Publications style
Liang C, Li X, Quan X and Zhang L: DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways. Exp Ther Med 25: 183, 2023.
APA
Liang, C., Li, X., Quan, X., & Zhang, L. (2023). DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways. Experimental and Therapeutic Medicine, 25, 183. https://doi.org/10.3892/etm.2023.11882
MLA
Liang, C., Li, X., Quan, X., Zhang, L."DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways". Experimental and Therapeutic Medicine 25.4 (2023): 183.
Chicago
Liang, C., Li, X., Quan, X., Zhang, L."DAB2 promotes pulmonary fibrosis and may act as an intermediate between IGF‑1R and PI3K/AKT signaling pathways". Experimental and Therapeutic Medicine 25, no. 4 (2023): 183. https://doi.org/10.3892/etm.2023.11882
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