Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases
Peroxisome proliferator activated receptor (PPAR)-γ is a nuclear hormone receptor that is activated by multiple agonists including thiazolidinediones, prostaglandins, and synthetic oleanolic acids. Many PPARγ ligands are under investigation as potential therapies for human diseases. These ligands mo...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/705352 |
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| author | Ajit A. Kulkarni Collynn F. Woeller Thomas H. Thatcher Sesquile Ramon Richard P. Phipps Patricia J. Sime |
| author_facet | Ajit A. Kulkarni Collynn F. Woeller Thomas H. Thatcher Sesquile Ramon Richard P. Phipps Patricia J. Sime |
| author_sort | Ajit A. Kulkarni |
| collection | DOAJ |
| description | Peroxisome proliferator activated receptor (PPAR)-γ is a nuclear hormone receptor that is activated by multiple agonists including thiazolidinediones, prostaglandins, and synthetic oleanolic acids. Many PPARγ ligands are under investigation as potential therapies for human diseases. These ligands modulate multiple cellular pathways via both PPARγ-dependent and PPARγ-independent mechanisms. Here, we review the role of PPARγ and PPARγ ligands in lung disease, with emphasis on PPARγ-independent effects. PPARγ ligands show great promise in moderating lung inflammation, as antiproliferative agents in combination to enhance standard chemotherapy in lung cancer and as treatments for pulmonary fibrosis, a progressive fatal disease with no effective therapy. Some of these effects occur when PPARγ is pharmaceutically antagonized or genetically PPARγ and are thus independent of classical PPARγ-dependent transcriptional control. Many PPARγ ligands demonstrate direct binding to transcription factors and other proteins, altering their function and contributing to PPARγ-independent inhibition of disease phenotypes. These PPARγ-independent mechanisms are of significant interest because they suggest new therapeutic uses for currently approved drugs and because they can be used as probes to identify novel proteins and pathways involved in the pathogenesis or treatment of disease, which can then be targeted for further investigation and drug development. |
| format | Article |
| id | doaj-art-c4494efac2bf49b2b174d05bad06f797 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-c4494efac2bf49b2b174d05bad06f7972025-02-03T05:59:13ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/705352705352Emerging PPARγ-Independent Role of PPARγ Ligands in Lung DiseasesAjit A. Kulkarni0Collynn F. Woeller1Thomas H. Thatcher2Sesquile Ramon3Richard P. Phipps4Patricia J. Sime5Division of Pulmonary and Critical Care, Department of Medicine, University of Rochester School of Medicine and Dentistry, Box 692, Rochester, NY 14642, USAThe Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Box 692, Rochester, NY 14642, USADivision of Pulmonary and Critical Care, Department of Medicine, University of Rochester School of Medicine and Dentistry, Box 692, Rochester, NY 14642, USAThe Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Box 692, Rochester, NY 14642, USAThe Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Box 692, Rochester, NY 14642, USADivision of Pulmonary and Critical Care, Department of Medicine, University of Rochester School of Medicine and Dentistry, Box 692, Rochester, NY 14642, USAPeroxisome proliferator activated receptor (PPAR)-γ is a nuclear hormone receptor that is activated by multiple agonists including thiazolidinediones, prostaglandins, and synthetic oleanolic acids. Many PPARγ ligands are under investigation as potential therapies for human diseases. These ligands modulate multiple cellular pathways via both PPARγ-dependent and PPARγ-independent mechanisms. Here, we review the role of PPARγ and PPARγ ligands in lung disease, with emphasis on PPARγ-independent effects. PPARγ ligands show great promise in moderating lung inflammation, as antiproliferative agents in combination to enhance standard chemotherapy in lung cancer and as treatments for pulmonary fibrosis, a progressive fatal disease with no effective therapy. Some of these effects occur when PPARγ is pharmaceutically antagonized or genetically PPARγ and are thus independent of classical PPARγ-dependent transcriptional control. Many PPARγ ligands demonstrate direct binding to transcription factors and other proteins, altering their function and contributing to PPARγ-independent inhibition of disease phenotypes. These PPARγ-independent mechanisms are of significant interest because they suggest new therapeutic uses for currently approved drugs and because they can be used as probes to identify novel proteins and pathways involved in the pathogenesis or treatment of disease, which can then be targeted for further investigation and drug development.http://dx.doi.org/10.1155/2012/705352 |
| spellingShingle | Ajit A. Kulkarni Collynn F. Woeller Thomas H. Thatcher Sesquile Ramon Richard P. Phipps Patricia J. Sime Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases PPAR Research |
| title | Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases |
| title_full | Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases |
| title_fullStr | Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases |
| title_full_unstemmed | Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases |
| title_short | Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases |
| title_sort | emerging pparγ independent role of pparγ ligands in lung diseases |
| url | http://dx.doi.org/10.1155/2012/705352 |
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