Lysine-specific demethylase-1 regulates fibroblast activation in pulmonary fibrosis via TGF-β1/Smad3 pathway

Pan, Xiaohua; Li, Jiahong; Tu, Xing; Wu, Chengfei; Liu, He; Luo, Yang; Dong, Xiaoliang; Xiu, Li; Pan, Li-Long; Sun, Jia

doi:10.1016/j.phrs.2019.104592

Cited by 39 publications

(22 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aberrant activation of fibroblast associated with excessive extracellular matrix accumulation is the main characteristic of pulmonary fibrosis [ 71 ]. As the master regulator of fibrosis, TGF-β1 could directly induce transcription of profibrotic molecules including α-SMA, fibronectin, and collagens via TGF-β1/Smad signaling during myofibroblast activation [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Cheng

Wang

et al. 2021

J Transl Med

View full text Add to dashboard Cite

Background Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. Methods The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models. Results At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2–10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. Conclusions In this study, we identified that metformin might be a potential drug for silicosis treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Cheng

Wang

et al. 2021

J Transl Med

View full text Add to dashboard Cite

show abstract

“…The aberrant activation of broblast associated with excessive extracellular matrix accumulation is the main characteristic of pulmonary brosis [59]. In this study, we found that the treatment of metformin signi cantly inhibited TGF-β1-induced myo broblast differentiation.…”

Section: Discussionmentioning

confidence: 50%

Metformin Attenuates Silica-induced Pulmonary Fibrosis via AMPK Signaling

Cheng

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis.Methods: The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. SiO2-stimulated lung epithelial cells/macrophages and TGF-β-induced differentiated lung fibroblasts were used for in vitro models.Results: At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2mM to 10mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway.Conclusions: In this study, we identified that metformin might be a potential drug for silicosis treatment.

show abstract

“…Smad2 and Smad3 act downstream of TGF- β 1, which promotes Smad2 and Smad3 phosphorylation when activated. Both proteins, which have a high homology, are subsequently transferred to the nucleus and regulate the expression of fibrosis-related target genes, such as α -SMA, to accelerate the progression of fibrosis [ 31 – 33 ]. The expression of p-Smad2 and p-Smad3 proteins is a marker of TGF- β 1/Smads signaling pathway activation [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Dendrobium Mixture Ameliorates Diabetic Nephropathy in db/db Mice by Regulating the TGF-β1/Smads Signaling Pathway

Chen

Lin

Zheng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-β1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-β1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway.

show abstract

Lysine-specific demethylase-1 regulates fibroblast activation in pulmonary fibrosis via TGF-β1/Smad3 pathway

Cited by 39 publications

References 37 publications

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Metformin Attenuates Silica-induced Pulmonary Fibrosis via AMPK Signaling

Dendrobium Mixture Ameliorates Diabetic Nephropathy in db/db Mice by Regulating the TGF-β1/Smads Signaling Pathway

Contact Info

Product

Resources

About