Pirfenidone protects against paraquat-induced lung injury and fibrosis in mice by modulation of inflammation, oxidative stress, and gene expression

Pourgholamhossein, Fateme; Rasooli, Rokhsana; Pournamdari, Mostafa; Pourgholi, Leyla; Fekri, Mitra Samareh; Ghazi‐Khansari, Mahmoud; Iranpour, Maryam; Poursalehi, Hamid-Reza; Heidari, Mahnaz; Mandegary, Ali

doi:10.1016/j.fct.2017.12.034

Cited by 78 publications

(60 citation statements)

References 50 publications

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“…Pirfenidone is a low molecular weight synthetic molecule that has antifibrotic properties in animal models; it suppresses production of ROS and downregulates genes encoding profibrotic cytokines, such as α-SMA, collagen I, and collagen IV. Pirfenidone upregulates regulator of G-protein signaling 2 (Xie et al, 2016;Li et al, 2018;Pourgholamhossein et al, 2018). Moreover, RamachandraRao et al (2009) found that pirfenidone decreased TGF-β promoter activity, blocked TGF-β1 production, and was effective in reducing mesangial matrix expansion and fibrosis in DKD.…”

Section: Tgf-β1 Signaling As a Therapeutic Strategy For Dkdmentioning

confidence: 99%

Transforming Growth Factor-Beta1 in Diabetic Kidney Disease

Zhao

Zou

Liu

2020

Front. Cell Dev. Biol.

102

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Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Renin-angiotensin-aldosterone system (RAAS) inhibitors and sodiumglucose co-transporter 2 (SGLT2) inhibitors have shown efficacy in reducing the risk of ESRD. However, patients vary in their response to RAAS blockades, and the pharmacodynamic responses to SGLT2 inhibitors decline with increasing severity of renal impairment. Thus, effective therapy for DKD is yet unmet. Transforming growth factor-β1 (TGF-β1), expressed by nearly all kidney cell types and infiltrating leukocytes and macrophages, is a pleiotropic cytokine involved in angiogenesis, immunomodulation, and extracellular matrix (ECM) formation. An overactive TGF-β1 signaling pathway has been implicated as a critical profibrotic factor in the progression of chronic kidney disease in human DKD. In animal studies, TGF-β1 neutralizing antibodies and TGF-β1 signaling inhibitors were effective in ameliorating renal fibrosis in DKD. Conversely, a clinical study of TGF-β1 neutralizing antibodies failed to demonstrate renal efficacy in DKD. However, overexpression of latent TGF-β1 led to anti-inflammatory and anti-fibrosis effects in non-DKD. This evidence implied that complete blocking of TGF-β1 signaling abolished its multiple physiological functions, which are highly associated with undesirable adverse events. Ideal strategies for DKD therapy would be either specific and selective inhibition of the profibrotic-related TGF-β1 pathway or blocking conversion of latent TGF-β1 to active TGF-β1.

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Section: Tgf-β1 Signaling As a Therapeutic Strategy For Dkdmentioning

confidence: 99%

Transforming Growth Factor-Beta1 in Diabetic Kidney Disease

Zhao

Zou

Liu

2020

Front. Cell Dev. Biol.

102

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“…Cancer is one of the most challenging disorders around the world (22)(23)(24)(25) and it appears that lung has a particular sensitivity to potentially toxic agents and damage, resulting in various lung disorders (26)(27)(28)(29). Gene therapy is considered a promising strategy in promoting the health of a number of inherited and acquired human conditions such as: cancer, diabetes, cardiovascular diseases and mental disorders (30).…”

Section: Discussionmentioning

confidence: 99%

ZEB1 and ZEB2 gene editing mediated by CRISPR/Cas9 in A549 cell line

Mohammadinejad¹,

Sassan²,

Pardakhty³

et al. 2020

BLL

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OBJECTIVES: One of the best approaches for recognition of protein function is the induction of mutations for a gene knockout. In line with this strategy, gene editing tools allow researchers to induce these mutations. Lung cancer is one of the leading causes of death worldwide. ZEB1 and ZEB2 genes are the candidates for this disease. METHODS: The ZEB1 and ZEB2 knockout in the non-small cell lung cancer cell line (A549 cell) was investigated. Purifi cation of recombination plasmids was performed from bacteria and then was transported to the A549 cell line. The deletion of ZEB1 and ZEB2 were examined by PCR. RESULTS: The results demonstrated the mutation and deletion in ZEB1 and ZEB2 genes. Based on the fi ndings of this study, A549 cells were transfected with the vectors carrying the sgRNA/Cas9, simultaneously. The DNA fragment demonstrated the presence of indels in target sites as well as provided the potential of CRISPR/Cas9 system. CONCLUSION: CRISPR/Cas9 offers a great potential as an effi cient technique for editing of ZEB1 and ZEB2 genes in A549 cell line (Tab. 1, Fig. 6, Ref.

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“…41 As already investigated in the ''pretrial era,'' some authors focused on the role of pirfenidone in mouse paraquat-induced lung fibrosis. In a first experimental study by Pourgholamhossein et al, 42 pirfenidone was shown to significantly decrease lung fibrosis, edema, inflammatory cell infiltration, TGF-b1 concentration, and the amount of hydroxyproline in the lung tissue. The authors demonstrated these effects through inhibition of inflammation and oxidative stress and down-regulation of genes encoding for profibrotic cytokines and enzymatic systems for reactive oxygen species (ROS) production.…”

Section: Pirfenidonementioning

confidence: 97%

“…Iyer et al, 17 1995 X Conte et al, 32 2014 X Iyer et al, 18 1999 X X Walter et al, 33 2014 X Iyer et al, 19 1999 X X Inomata et al, 34 2014 X Iyer et al, 20 2000 X X Bauer et al, 35 2015 X Kehrer & Margolin, 21 1997 X Neri et al, 36 2016 Antioxidant Card et al, 22 2003 X X Liu et al, 37 2017 X X Antioxidant Kakugawa et al, 23 2004 X X Xie et al, 38 2016 X Nakayama et al, 24 2008 X Yu et al, 39 2017 X X Hisatomi et al, 25 2012 X Didiasova et al, 40 2017 X Liu et al, 26 2005 X Kurita et al, 41 2017 X X Oku et al, 27 2008 X X Pourgholamhossei et al, 42 2017 X X Antioxidant Seifirad et al, 28 2012 X Rasooli et al, 43 2018 X Watanabe et al, 29 2013 X X Nintedanib Chaudhary et al, 30 2007 X Wollin et al, 44 2014 X X Hostettler et al, 45 2014 X Kamio et al, 46 2015…”

Section: Pirfenidonementioning

confidence: 99%

“…The authors demonstrated these effects through inhibition of inflammation and oxidative stress and down-regulation of genes encoding for profibrotic cytokines and enzymatic systems for reactive oxygen species (ROS) production. 42 More recently, the same research group used a combination therapy of pirfenidone-prednisolone versus only pirfenidone, concluding that the combined therapy could represent a more powerful therapeutic approach in reducing paraquat-induced lung fibrosis. 43…”

Section: Pirfenidonementioning

confidence: 99%

See 1 more Smart Citation

Idiopathic Pulmonary Fibrosis and Antifibrotic Treatments: Focus on Experimental Studies

Lunardi¹,

Pezzuto²,

Vuljan³

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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- Pirfenidone has a longer history of preclinical experimental studies than nintedanib. Many studies have been reported more recently (after 2014) and some of them evaluated the association of both drugs, thus suggesting their combination in future therapeutic approaches. Future investigations focusing on targets at molecular, cellular, and tissue levels are necessary to have a better in-depth knowledge of the properties of these drugs and to explore the potential efficacy of both or other drug combinations.

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Pirfenidone protects against paraquat-induced lung injury and fibrosis in mice by modulation of inflammation, oxidative stress, and gene expression

Cited by 78 publications

References 50 publications

Transforming Growth Factor-Beta1 in Diabetic Kidney Disease

Transforming Growth Factor-Beta1 in Diabetic Kidney Disease

ZEB1 and ZEB2 gene editing mediated by CRISPR/Cas9 in A549 cell line

Idiopathic Pulmonary Fibrosis and Antifibrotic Treatments: Focus on Experimental Studies

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