Total extract of Yupingfeng attenuates bleomycin-induced pulmonary fibrosis in rats

Li, Liucheng; Li, Delin; Xu, Liang; Zhao, Ping; Deng, Zhiping; Mo, Xiaoting; Li, Ping; Qi, Lian‐Wen; Li, Jun; Gao, Jian

doi:10.1016/j.phymed.2014.10.011

Cited by 48 publications

(28 citation statements)

References 23 publications

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“…Hematoxylin and eosin (H&E), Masson’s trichrome and immunohistochemistry (IHC) staining were performed as previously described303132. Briefly, lung tissues were fixed using 10% formaldehyde solutions for 24 h, followed by paraffin-embedding, and the paraffin blocks were cut at 5 μm using microtome.…”

Section: Methodsmentioning

confidence: 99%

Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis

Zhou

Cui

et al. 2016

Sci Rep

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Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2−/−) and wild-type mice to compare the development of PF. Rat type II alveolar epithelial cells (RLE-6TN) were treated with a specific Nrf2 activator sulforaphane, or transfected with Nrf2 and snail siRNAs to determine their effects on transforming growth factor β1 (TGF-β1)-induced EMT. We found that BLM-induced EMT and lung fibrosis were more severe in Nrf2−/− mice compared to wild-type mice. In vitro, sulforaphane treatment attenuated TGF-β1-induced EMT, accompanied by the down-regulation of snail. Inversely, silencing Nrf2 by siRNA enhanced TGF-β1-induced EMT along with increased expression of snail. Interestingly, when snail was silenced by siRNA, sulforaphane treatment was unable to reduce the progression of EMT in RLE-6TN cells. These findings suggest that Nrf2 attenuates EMT and fibrosis process by regulating the expression of snail in PF.

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Section: Methodsmentioning

confidence: 99%

Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis

Zhou

Cui

et al. 2016

Sci Rep

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“…Thus, further experiments are required to understand whether the activation of HMGB1 takes part in a non-Smad signaling pathway, the mitogen-activated protein kinase signaling pathway, in tissue fibrosis (Mishra et al, 2014). Despite current data supporting the profibrotic role of HMGB1 in PF, and recent studies showing that reducing the abnormal expression of HMGB1 attenuates PF in rats (Li et al, 2015;Zhang et al, 2015), the protective role of HMGB1 inhibitors in PF remains to be further identified. Additionally, more detailed studies of TGF-b1/Smad signaling inhibitors should be performed to confirm the interplay HMGB1 Mediates EMT via TGF-b1/Smad2/3 Signaling in PF between the HMGB1 signaling and the TGF-b1/Smad signaling pathway.…”

Section: Hmgb1 Mediates Emt Via Tgf-b1/smad2/3 Signaling In Pfmentioning

confidence: 99%

High-Mobility Group Box 1 Mediates Epithelial-to-Mesenchymal Transition in Pulmonary Fibrosis Involving Transforming Growth Factor-β1/Smad2/3 Signaling

et al. 2015

J Pharmacol Exp Ther

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Epithelial-to-mesenchymal transition (EMT) is a crucial event in the cellular origin of myofibroblasts that secrete extracellular matrix in the progression of pulmonary fibrosis (PF). Highmobility group box 1 (HMGB1) is a novel mediator of EMT. However, whether this process involves the recognized transforming growth factor-b1 (TGF-b1)/Smad signaling that also contributes to EMT in PF has not yet been elucidated. Here, we developed a model of PF induced by bleomycin (BLM) in rats and conducted several simulation experiments in A549 (human) and RLE-6TN (rat) alveolar epithelial cell (AEC) lines to unravel the role of TGF-b1/Smad2/3 signaling in HMGB1-mediated EMT. We found that the levels of serum HMGB1 and lung hydroxyproline were severely elevated after BLM administration. Moreover, the protein expression of HMGB1, TGF-b1, phosphorylated Smad2/3 (p-Smad2/3), and mesenchymal markers including a-smooth muscle actin, vimentin, and type I collagen were significantly increased with the reduced protein expression of an epithelial marker (E-cadherin) in the rat model by Western blot or immunohistochemical analysis. In addition, the uptake of both exogenous TGF-b1 and HMGB1 by AECs could induce EMT; meanwhile, HMGB1 dramatically enhanced TGF-b1 expression and triggered Smad2/3 phosphorylation. In contrast, TGF-b1 deficiency evidently ameliorated HMGB1-mediated EMT with reduced p-Smad2/3 in A549 cells. It provides new insights that HMGB1 release from injured lungs promotes AEC damage through induction of the EMT process, in which TGF-b1/Smad2/3 signaling is activated and contributes to PF. These results suggest that HMGB1 may constitute a therapeutic target for developing antifibrotic agents for abnormal lung remodeling.

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“…Our previous studies have showed that YPF-G has antiinflammation and immunoregulation activities. Simultaneously, we discovered various inflammatory mediator factors could be targeted to ECM and regulate cellular functions involved in PF, but the impact of YPF-G and its mechanism involved in PF are nubilous [22,23]. Whether the protective effect of YPF-G is associated with interfering HMGB1 activation and EMT, there is no final conclusion.…”

Section: Introductionmentioning

confidence: 99%

Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial–mesenchymal transition

Cui

et al. 2015

Inflamm. Res.

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Total extract of Yupingfeng attenuates bleomycin-induced pulmonary fibrosis in rats

Cited by 48 publications

References 23 publications

Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis

Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis

High-Mobility Group Box 1 Mediates Epithelial-to-Mesenchymal Transition in Pulmonary Fibrosis Involving Transforming Growth Factor-β1/Smad2/3 Signaling

Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial–mesenchymal transition

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