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Open Access | 10.1172/jci.insight.158100
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Ahangari, F.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Price, N.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Chioccioli, M.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Adams, T.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Cosme Jr, C.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Rose, K.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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McDonough, J.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Ibarra, G.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Omote, N.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Schupp, J.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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DeIuliis, G.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Villalba Nunez, J.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Sharma, L.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Ryu, C.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Dela Cruz, C.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Liu, X.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Prasse, A.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Rosas, I.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Fernandez-Hernando, C.
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1Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, United States of America
2Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
3Department of Pharmaceutical Sciences, University of Connecticut, Storrs, United States of America
4Yale University School of Medicine, New Haven, United States of America
5Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
6Department of Cell Biology, Yale University School of Medicine, New Haven, United States of America
7Department of Pneumology, Hannover Medical School (MHH), Hannover, Germany
8Department of Medicine, Baylor College of Medicine, Houston, Houston, United States of America
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Published January 10, 2023 - More info
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Recent findings have shown a marked metabolic reprogramming associated with changes in mitochondrial homeostasis and autophagy during pulmonary fibrosis. The microRNA-33 (miR-33) family of microRNAs (miRNAs) encoded within the introns of SREBP (sterol regulatory element binding protein) genes are master regulators of sterol and fatty acid (FA) metabolism. miR-33 controls macrophage immuno-metabolic response and enhances mitochondrial biogenesis, FA oxidation, and cholesterol efflux. Here, we show that miR-33 levels are increased in Broncho Alveolar Lavage (BAL) cells isolated from IPF patients compared to healthy controls. We demonstrate that specific genetic ablation of miR-33 in macrophages protects against bleomycin-induced pulmonary fibrosis. The absence of miR-33 in macrophages improves mitochondrial homeostasis and increases autophagy while decreasing inflammatory response after bleomycin injury. Notably, pharmacological inhibition of miR-33 in macrophages via administration of anti-miR-33 Peptide Nucleic Acids (PNA-33) attenuates fibrosis in different in vivo and ex vivo mice and human models of pulmonary fibrosis. Together, these studies elucidate a major role of miR-33 in macrophages in the regulation of pulmonary fibrosis and uncover a novel therapeutic approach to treat this disease.