Role of pirfenidone in the management of pulmonary fibrosis

Meyer, Keith C.; Decker, Catherine A

doi:10.2147/tcrm.s81141

Cited by 55 publications

(38 citation statements)

References 62 publications

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“…The successful development of this comprehensive fibrosis model motivated us to test its capabilities in screening for anti-fibrogenic small molecule compounds. As a proof of concept, pirfenidone was selected based on its clinical relevance 43 , 44 and its documented ability to inhibit TGFβ1-induced fibrogenesis 45 , 46 . Notably, as little as 24 hours pirfenidone treatment of the co-culture resulted in significantly decreased myofibroblast activation as shown by reduced amount of αSMA in fibroblasts (Fig.…”

Section: Resultsmentioning

confidence: 99%

Monitoring and manipulating cellular crosstalk during kidney fibrosis inside a 3D in vitro co-culture

Nugraha

Mohr

Ponti

et al. 2017

Sci Rep

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In pharmacological research the development of promising lead compounds requires a detailed understanding of the dynamics of disease progression. However, for many diseases, such as kidney fibrosis, gaining such understanding requires complex real-time, multi-dimensional analysis of diseased and healthy tissue. To allow for such studies with increased throughput we established a dextran hydrogel-based in vitro 3D co-culture as a disease model for kidney fibrosis aimed at the discovery of compounds modulating the epithelial/mesenchymal crosstalk. This platform mimics a simplified pathological renal microenvironment at the interface between tubular epithelial cells and surrounding quiescent fibroblasts. We combined this 3D technology with epithelial reporter cell lines expressing fluorescent biomarkers in order to visualize pathophysiological cell state changes resulting from toxin-mediated chemical injury. Epithelial cell damage onset was robustly detected by image-based monitoring, and injured epithelial spheroids induced myofibroblast differentiation of co-cultured quiescent human fibroblasts. The presented 3D co-culture system therefore provides a unique model system for screening of novel therapeutic molecules capable to interfere and modulate the dialogue between epithelial and mesenchymal cells.

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Section: Resultsmentioning

confidence: 99%

Monitoring and manipulating cellular crosstalk during kidney fibrosis inside a 3D in vitro co-culture

Nugraha

Mohr

Ponti

et al. 2017

Sci Rep

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“…Indeed, nintedanib and pirfenidone were clinically tried and evaluated to delay the progression of fibrosis 4 , 5 . However, these drugs were reported to provoke serious adverse effects in the clinical trial 6 – 8 .…”

Section: Introductionmentioning

confidence: 99%

Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis

et al. 2018

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While wound healing is completed, the epithelium functions to normalize the interstitial context by eliminating fibroblasts excited during matrix reconstruction. If not, tissues undergo pathologic fibrosis. Pulmonary fibrosis is a fatal and hardly curable disorder. We here tried to identify epithelium-derived cytokines capable of ameliorating pulmonary fibrosis. Human lung fibroblasts were inactivated in epithelial cell-conditioned media. Cystatin C (CST3) and growth differentiation factor 15 (GDF15) were found to be enriched in the conditioned media and to inhibit the growth and activation of lung fibroblasts by inactivating the TGF–Smad pathway. In mouse and human lungs with interstitial fibrosis, CST3 and GDF15 expressions were markedly reduced, and the restoration of these cytokines alleviated the fibrotic changes in mouse lungs. These results suggest that CST3 and GDF15 are bona fide regulators to prevent excessive proliferation and activation of fibroblasts in injured lungs. These cytokines could be potential therapeutics for ameliorating interstitial lung fibrosis.

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“…Пирфенидон -низкомолекулярный препарат, примененный впервые для терапии идиопатического легочного фиброза, показал хороший клинический эффект [12,13]. По данным исследований, действие пирфенидона основано на угнетении синтеза ряда цитокинов и факторов роста, ответственных за индукцию процесса фиброза [14,15].…”

Section: обоснованиеunclassified

Evaluation of antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture

Atkova¹,

Krakhovetskiy²,

Yartsev³

et al. 2018

Annals RAMS

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Background:One of the main reasons for failure of surgical treatment of primary acquired nasolacrimal duct obstruction is excessive postoperative scarring of the dacryostomy. Despite the variety of procedures designed to prevent this, conflicting evidence of their efficacy and safety provide incentive for further research of adjunctive therapy with antifibrotic agents in dacryocystorhinostomy. Aims: To evaluate the antifibrotic effect of pirfenidone on cultured human nasal mucosa fibroblasts. Materials and methods: Samples for cultured human nasal mucosa fibroblasts were obtained from 3 consecutive patients during the endonasal endoscopic dacryocystorhinostomy. Cell viability following treatment with pirfenidone was evaluated using MTS-assay. Induced inhibition of cell proliferation and migration was determined by scratch wound assay. Results: In this study pirfenidone exhibited a significant dose-dependent inhibiting effect on fibroblast proliferation with insignificant cell toxicity. Cell viability after 48 hours of incubation with various pirfenidone concentrations did not drop below 80%. The recovery of the fibroblast monolayer assessed after 24 hours of incubation was 84.88 and 8.26% in the control group, at a drug concentration of 0.15 mg/ml. Cell proliferation and migration was severely inhibited in cell culture specimens treated with pirfenidone compared to controls. The difference between groups was statistically significant (p=0.001). Conclusions: In our study pirfenidone demonstrated a pronounced antifibrotic effect. It is unlikely that inhibition of proliferation and migration of human nasal mucosa fibroblasts is mediated by cell toxicity of this medication as it was evaluated as low. Nonetheless, an in vitro analysis is insufficient to assess the efficacy and safety of pirfenidone in preventing cicatrix formation following dacrycystorhinostomy. Научно-исследовательский институт глазных болезней, Москва, Российская Федерация Изучение антифибротических свойств препарата пирфенидон на клеточной культуре фибробластов слизистой оболочки полости носа Обоснование. Одной из основных причин неудачи в хирургическом лечении дакриоцистита является рубцовое заращение дакриостомысоустья между слезным мешком и полостью носа. Несмотря на наличие большого количества предложенных средств и методик профилактики этого явления, литературные данные свидетельствуют об отсутствии надежных методов, позволяющих предотвратить рубцевание дакриостомы в послеоперационном периоде, что обусловливает необходимость продолжения исследований в данном направлении. Цель исследования -изучение антифибротических свойств препарата пирфенидон на клеточной культуре фибробластов слизистой оболочки полости носа. Методы. Клетки для культуры фибробластов слизистой оболочки полости носа были получены у 3 пациентов во время эндоназальной эндоскопической дакриоцисториностомии. Токсичность препарата в концентрациях от 0,01 до 0,5 мг/мл была исследована при помощи теста с MTS-реагентом. Ингибирующий эффект пирфенидона на миграцию фибробластов оценивал...

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Role of pirfenidone in the management of pulmonary fibrosis

Cited by 55 publications

References 62 publications

Monitoring and manipulating cellular crosstalk during kidney fibrosis inside a 3D in vitro co-culture

Monitoring and manipulating cellular crosstalk during kidney fibrosis inside a 3D in vitro co-culture

Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis

Evaluation of antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture

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