In the present study, both treatment regimens effectively inhibited lung fibrosis through several pathways, suppressing tumor growth factor-β (TGF-β)/SMAD3 expression which is considered the master signaling pathway.
Hesperidin alleviates BLM-induced IPF via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways which in turn ameliorate the modulation of oxido-inflammatory markers (Nrf2 and HO-1) and pro-inflammatory markers (TNF-α, IL-1β, and IL-6) to reduce collagen deposition during pulmonary fibrosis.See also Figure 1(Fig.1).
Meanwhile, SMOC2<sup>-/-</sup> suppressed the progression of pulmonary fibrosis, as evidenced by the reduction in levels of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), p-SMAD2 and p-SMAD3 in lung tissue samples.
Finally, using an adenoviral TGFβ1 over-expression model of pulmonary fibrosis we demonstrate that Smad3 is crucial for TGFβ1-induced αvβ6 integrin expression within the alveolar epithelium in vivo.
We postulate that these developmental epigenetic mechanisms by which Smad3 regulates MMP9 transcription cell autonomously may be important in modulating both emphysema and pulmonary fibrosis and that this could explain why both pathologies can appear within the same lung specimen.
CYLD inhibited transforming growth factor-β-signalling and prevented lung fibrosis by decreasing the stability of Smad3 in an E3 ligase carboxy terminus of Hsc70-interacting protein-dependent manner.
The expression levels of α-SMA, p-FGFRs, p-ERK1/2 and p-Smad3 in the lungs of sFGFR2c-treated mice were markedly lower. sFGFR2c may have potential for the treatment of lung fibrosis as an FGF-2 antagonist.
In this study we investigate whether inflammation induced by IL-1beta is able to independently induce lung fibrosis in mice deficient in the Smad3 gene.