The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives
Interstitial lung diseases (ILDs) are a heterogeneous group of pulmonary disorders characterized by variable degrees of inflammation, interstitial thickening, and fibrosis leading to distortion of the pulmonary architecture and gas exchange impairment. Among them, idiopathic pulmonary fibrosis (IPF)...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/547 |
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| author | Sara Lettieri Francesco R. Bertuccio Lucia del Frate Fabio Perrotta Angelo G. Corsico Giulia M. Stella |
| author_facet | Sara Lettieri Francesco R. Bertuccio Lucia del Frate Fabio Perrotta Angelo G. Corsico Giulia M. Stella |
| author_sort | Sara Lettieri |
| collection | DOAJ |
| description | Interstitial lung diseases (ILDs) are a heterogeneous group of pulmonary disorders characterized by variable degrees of inflammation, interstitial thickening, and fibrosis leading to distortion of the pulmonary architecture and gas exchange impairment. Among them, idiopathic pulmonary fibrosis (IPF) displays the worst prognosis. The only therapeutic options consist of the two antifibrotic drugs, pirfenidone and nintedanib, which limit fibrosis progression but do not reverse the lung damage. The shift of the pathogenetic paradigm from inflammatory disease to epithelium-derived disease has definitively established the primary role of type II alveolar cells, which lose their epithelial phenotype and acquire a mesenchymal phenotype with production of collagen and extracellular matrix (EMC) deposition. Some predisposing environmental and genetic factors (e.g., smoke, pollution, gastroesophageal reflux, variants of telomere and surfactant genes) leading to accelerated senescence set a pro-fibrogentic microenvironment and contribute to the loss of regenerative properties of type II epithelial cells in response to pathogenic noxae. This review provides a complete overview of the different pathogenetic mechanisms leading to the development of IPF. Then, we summarize the currently approved therapies and the main clinical trials ongoing. Finally, we explore the potentialities offered by agents not only interfering with the processes of fibrosis but also restoring the physiological properties of alveolar regeneration, with a particular focus on potentialities and concerns about cell therapies based on mesenchymal stem cells (MSCs), whose anti-inflammatory and immunomodulant properties have been exploited in other fibrotic diseases, such as graft versus host disease (GVHD) and COVID-19-related ARDS. |
| first_indexed | 2024-03-08T15:04:40Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:04:40Z |
| publishDate | 2023-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-74996280bc894362abbad7341347d2562024-01-10T14:59:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125154710.3390/ijms25010547The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic PerspectivesSara Lettieri0Francesco R. Bertuccio1Lucia del Frate2Fabio Perrotta3Angelo G. Corsico4Giulia M. Stella5Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, ItalyDepartment of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, ItalyDepartment of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, ItalyDepartment of Translational Medical Science, University of Campania Luigi Vanvitelli, 80055 Naples, ItalyDepartment of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, ItalyDepartment of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, ItalyInterstitial lung diseases (ILDs) are a heterogeneous group of pulmonary disorders characterized by variable degrees of inflammation, interstitial thickening, and fibrosis leading to distortion of the pulmonary architecture and gas exchange impairment. Among them, idiopathic pulmonary fibrosis (IPF) displays the worst prognosis. The only therapeutic options consist of the two antifibrotic drugs, pirfenidone and nintedanib, which limit fibrosis progression but do not reverse the lung damage. The shift of the pathogenetic paradigm from inflammatory disease to epithelium-derived disease has definitively established the primary role of type II alveolar cells, which lose their epithelial phenotype and acquire a mesenchymal phenotype with production of collagen and extracellular matrix (EMC) deposition. Some predisposing environmental and genetic factors (e.g., smoke, pollution, gastroesophageal reflux, variants of telomere and surfactant genes) leading to accelerated senescence set a pro-fibrogentic microenvironment and contribute to the loss of regenerative properties of type II epithelial cells in response to pathogenic noxae. This review provides a complete overview of the different pathogenetic mechanisms leading to the development of IPF. Then, we summarize the currently approved therapies and the main clinical trials ongoing. Finally, we explore the potentialities offered by agents not only interfering with the processes of fibrosis but also restoring the physiological properties of alveolar regeneration, with a particular focus on potentialities and concerns about cell therapies based on mesenchymal stem cells (MSCs), whose anti-inflammatory and immunomodulant properties have been exploited in other fibrotic diseases, such as graft versus host disease (GVHD) and COVID-19-related ARDS.https://www.mdpi.com/1422-0067/25/1/547fibrosisregenerationmesenchymal stem cells |
| spellingShingle | Sara Lettieri Francesco R. Bertuccio Lucia del Frate Fabio Perrotta Angelo G. Corsico Giulia M. Stella The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives International Journal of Molecular Sciences fibrosis regeneration mesenchymal stem cells |
| title | The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives |
| title_full | The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives |
| title_fullStr | The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives |
| title_full_unstemmed | The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives |
| title_short | The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives |
| title_sort | plastic interplay between lung regeneration phenomena and fibrotic evolution current challenges and novel therapeutic perspectives |
| topic | fibrosis regeneration mesenchymal stem cells |
| url | https://www.mdpi.com/1422-0067/25/1/547 |
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