Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosis
Abstract Background Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the eff...
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| Format: | Article |
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BMC
2022-08-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-022-02116-4 |
| _version_ | 1828326286395703296 |
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| author | Christina Hesse Valerie Beneke Sebastian Konzok Claudia Diefenbach Jannie Marie Bülow Sand Sarah Rank Rønnow Morten Asser Karsdal Danny Jonigk Katherina Sewald Armin Braun Diana Julie Leeming Lutz Wollin |
| author_facet | Christina Hesse Valerie Beneke Sebastian Konzok Claudia Diefenbach Jannie Marie Bülow Sand Sarah Rank Rønnow Morten Asser Karsdal Danny Jonigk Katherina Sewald Armin Braun Diana Julie Leeming Lutz Wollin |
| author_sort | Christina Hesse |
| collection | DOAJ |
| description | Abstract Background Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the effects of two antifibrotic drugs: nintedanib and pirfenidone. Methods Precision-cut lung slices (PCLS) were prepared from bleomycin-treated rats or patients with PF. PCLS were incubated with nintedanib or pirfenidone for 48 h, and levels of neoepitope biomarkers of type I, III and VI collagen formation or degradation (PRO-C1, PRO-C3, PRO-C6 and C3M) as well as fibronectin (FBN-C) were assessed in the culture supernatants. Results In rat PCLS, incubation with nintedanib led to a reduction in C3M, reflecting type III collagen degradation. In patient PCLS, incubation with nintedanib reduced the levels of PRO-C3 and C3M, thus showing effects on both formation and degradation of type III collagen. Incubation with pirfenidone had a marginal effect on PRO-C3. There were no other notable effects of either nintedanib or pirfenidone on the other neoepitope biomarkers studied. Conclusions This study demonstrated that nintedanib modulates neoepitope biomarkers of type III collagen turnover and indicated that C3M is a promising translational neoepitope biomarker of PF in terms of therapy assessment. |
| first_indexed | 2024-04-13T19:36:23Z |
| format | Article |
| id | doaj.art-34a29ce6a5e24095888c0b8a45b0960c |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-13T19:36:23Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-34a29ce6a5e24095888c0b8a45b0960c2022-12-22T02:33:00ZengBMCRespiratory Research1465-993X2022-08-012311910.1186/s12931-022-02116-4Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosisChristina Hesse0Valerie Beneke1Sebastian Konzok2Claudia Diefenbach3Jannie Marie Bülow Sand4Sarah Rank Rønnow5Morten Asser Karsdal6Danny Jonigk7Katherina Sewald8Armin Braun9Diana Julie Leeming10Lutz Wollin11Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of German Center for Lung Research (DZL)Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of German Center for Lung Research (DZL)Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of German Center for Lung Research (DZL)Translational Medicine + Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KGNordic Bioscience A/S, Biomarkers & ResearchNordic Bioscience A/S, Biomarkers & ResearchNordic Bioscience A/S, Biomarkers & ResearchInstitute of Pathology, Hannover Medical SchoolFraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of German Center for Lung Research (DZL)Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of German Center for Lung Research (DZL)Nordic Bioscience A/S, Biomarkers & ResearchTranslational Medicine + Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KGAbstract Background Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the effects of two antifibrotic drugs: nintedanib and pirfenidone. Methods Precision-cut lung slices (PCLS) were prepared from bleomycin-treated rats or patients with PF. PCLS were incubated with nintedanib or pirfenidone for 48 h, and levels of neoepitope biomarkers of type I, III and VI collagen formation or degradation (PRO-C1, PRO-C3, PRO-C6 and C3M) as well as fibronectin (FBN-C) were assessed in the culture supernatants. Results In rat PCLS, incubation with nintedanib led to a reduction in C3M, reflecting type III collagen degradation. In patient PCLS, incubation with nintedanib reduced the levels of PRO-C3 and C3M, thus showing effects on both formation and degradation of type III collagen. Incubation with pirfenidone had a marginal effect on PRO-C3. There were no other notable effects of either nintedanib or pirfenidone on the other neoepitope biomarkers studied. Conclusions This study demonstrated that nintedanib modulates neoepitope biomarkers of type III collagen turnover and indicated that C3M is a promising translational neoepitope biomarker of PF in terms of therapy assessment.https://doi.org/10.1186/s12931-022-02116-4Antifibrotic therapyCollagenExtracellular matrixHuman lungPrecision-cut lung slicesNeoepitope biomarkers |
| spellingShingle | Christina Hesse Valerie Beneke Sebastian Konzok Claudia Diefenbach Jannie Marie Bülow Sand Sarah Rank Rønnow Morten Asser Karsdal Danny Jonigk Katherina Sewald Armin Braun Diana Julie Leeming Lutz Wollin Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosis Respiratory Research Antifibrotic therapy Collagen Extracellular matrix Human lung Precision-cut lung slices Neoepitope biomarkers |
| title | Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosis |
| title_full | Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosis |
| title_fullStr | Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosis |
| title_full_unstemmed | Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosis |
| title_short | Nintedanib modulates type III collagen turnover in viable precision-cut lung slices from bleomycin-treated rats and patients with pulmonary fibrosis |
| title_sort | nintedanib modulates type iii collagen turnover in viable precision cut lung slices from bleomycin treated rats and patients with pulmonary fibrosis |
| topic | Antifibrotic therapy Collagen Extracellular matrix Human lung Precision-cut lung slices Neoepitope biomarkers |
| url | https://doi.org/10.1186/s12931-022-02116-4 |
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