The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway
IntroductionIn addition to the traditional activation of resident receptors by release of local mediators, new evidence favors the existence of exosomes in cell-to-cell communication that mediates delivery of specific cargo to modulate recipient cell function. We report that mast cell exosomes are a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1139397/full |
| _version_ | 1797897131803017216 |
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| author | Alexandria Savage Cristobal Risquez Cristobal Risquez Kazunori Gomi Ryan Schreiner Alain C. Borczuk Stefan Worgall Stefan Worgall Stefan Worgall Randi B. Silver |
| author_facet | Alexandria Savage Cristobal Risquez Cristobal Risquez Kazunori Gomi Ryan Schreiner Alain C. Borczuk Stefan Worgall Stefan Worgall Stefan Worgall Randi B. Silver |
| author_sort | Alexandria Savage |
| collection | DOAJ |
| description | IntroductionIn addition to the traditional activation of resident receptors by release of local mediators, new evidence favors the existence of exosomes in cell-to-cell communication that mediates delivery of specific cargo to modulate recipient cell function. We report that mast cell exosomes are an additional source of pro-fibrotic substances and constitute a unique pathway for the generation of excess collagen.MethodsWe use primary human lung fibroblasts (HLFs) to demonstrate the uptake of labeled exosomes isolated from the human mast cell line HMC-1 (MC-EXOs), previously shown to contain protein cargo in common with human mast cell exosomes.ResultsThe MC-EXO uptake by HLF is to the cytosol and increases both proline hydroxylation in HLF lysate and secreted collagen, within 24 h, which is sustained over 72 h, the same time required for transforming growth factor-β (TGF-β) to activate collagen synthesis in the HLFs. Unlike TGF-β, MC-EXO uptake does not induce fibrillar gene activation or invoke the Smad-nuclear transcription pathway. We show that MC-EXO uptake and TGF-β have an additive effect on collagen synthesis in HLF and postulate that MC-EXO uptake by HLFs is a contributing factor to excess collagen synthesis and represents a unique paradigm for understanding fibrosis.DiscussionIt is known that, in the lungs, mast cells are more activated and increase in number with inflammation, injury and viral infection associated with fibrosis. With the reported increased incidence of post-COVID-pulmonary fibrosis (PCPF), data from patients with severe COVID-19 are presented that show an increase in the mast cell number in lung parenchyma, the site of PCPF. Our findings provide a rationale for targeting multiple fibrogenic pathways in the management of lung fibrosis and the use of mast cell exosomes as a biomarker for the prognostic and diagnostic management of evolving fibrotic lung disease. |
| first_indexed | 2024-04-10T07:53:53Z |
| format | Article |
| id | doaj.art-1cb99ceb4853466395190d40fd29eec2 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-10T07:53:53Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-1cb99ceb4853466395190d40fd29eec22023-02-23T06:55:25ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-02-011010.3389/fmed.2023.11393971139397The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathwayAlexandria Savage0Cristobal Risquez1Cristobal Risquez2Kazunori Gomi3Ryan Schreiner4Alain C. Borczuk5Stefan Worgall6Stefan Worgall7Stefan Worgall8Randi B. Silver9Silver Laboratory, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United StatesSilver Laboratory, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United StatesDivision of Pulmonary, Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY, United StatesSilver Laboratory, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United StatesDivision of Regenerative Medicine, Department of Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Weill Cornell Medicine, New York, NY, United StatesDepartment of Pathology and Laboratory Medicine, New York Presbyterian Hospital-Weill Cornell Medicine, New York, NY, United StatesDepartment of Pediatrics, Weill Cornell Medicine, New York, NY, United StatesDepartment of Genetic Medicine, Weill Cornell Medicine, New York, NY, United StatesDrukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY, United StatesSilver Laboratory, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United StatesIntroductionIn addition to the traditional activation of resident receptors by release of local mediators, new evidence favors the existence of exosomes in cell-to-cell communication that mediates delivery of specific cargo to modulate recipient cell function. We report that mast cell exosomes are an additional source of pro-fibrotic substances and constitute a unique pathway for the generation of excess collagen.MethodsWe use primary human lung fibroblasts (HLFs) to demonstrate the uptake of labeled exosomes isolated from the human mast cell line HMC-1 (MC-EXOs), previously shown to contain protein cargo in common with human mast cell exosomes.ResultsThe MC-EXO uptake by HLF is to the cytosol and increases both proline hydroxylation in HLF lysate and secreted collagen, within 24 h, which is sustained over 72 h, the same time required for transforming growth factor-β (TGF-β) to activate collagen synthesis in the HLFs. Unlike TGF-β, MC-EXO uptake does not induce fibrillar gene activation or invoke the Smad-nuclear transcription pathway. We show that MC-EXO uptake and TGF-β have an additive effect on collagen synthesis in HLF and postulate that MC-EXO uptake by HLFs is a contributing factor to excess collagen synthesis and represents a unique paradigm for understanding fibrosis.DiscussionIt is known that, in the lungs, mast cells are more activated and increase in number with inflammation, injury and viral infection associated with fibrosis. With the reported increased incidence of post-COVID-pulmonary fibrosis (PCPF), data from patients with severe COVID-19 are presented that show an increase in the mast cell number in lung parenchyma, the site of PCPF. Our findings provide a rationale for targeting multiple fibrogenic pathways in the management of lung fibrosis and the use of mast cell exosomes as a biomarker for the prognostic and diagnostic management of evolving fibrotic lung disease.https://www.frontiersin.org/articles/10.3389/fmed.2023.1139397/fullmast cellsexosomesfibroblastslungfibrosis |
| spellingShingle | Alexandria Savage Cristobal Risquez Cristobal Risquez Kazunori Gomi Ryan Schreiner Alain C. Borczuk Stefan Worgall Stefan Worgall Stefan Worgall Randi B. Silver The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway Frontiers in Medicine mast cells exosomes fibroblasts lung fibrosis |
| title | The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway |
| title_full | The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway |
| title_fullStr | The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway |
| title_full_unstemmed | The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway |
| title_short | The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway |
| title_sort | mast cell exosome fibroblast connection a novel pro fibrotic pathway |
| topic | mast cells exosomes fibroblasts lung fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1139397/full |
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